Thallium-201 stress-redistribution myocardial rotational tomography: development of criteria for visual interpretation.
Despite high sensitivity and specificity for overall detection of coronary artery disease (CAD), planar stress-redistribution thallium-201 (Tl-201) scintigraphy remains suboptimal in localizing disease, because of overlap of myocardial segments. Single photon emission computerized tomography (SPECT), by providing three-dimensional representation of myocardial Tl-201, offers promise for improved localization of CAD. In 50 consecutive patients (22 normal and 28 with CAD), who underwent SPECT stress-redistribution Tl-201 imaging, we systemically developed visual interpretive criteria for perfusion abnormality on SPECT. For overall detection of disease, the best criterion for abnormality was greater than or equal to 8 sectors of moderately decreased Tl-201 uptake. With this criterion, the true positive and true negative rates for overall detection of disease were 96% and 91%, respectively. The best criterion for significant defect in the anterior or posterior coronary circulation was greater than or equal to 3 sectors of moderately decreased Tl-201 uptake. With this criterion, the true positive and true negative rates for anterior circulation disease were 71% and 100%, respectively. With respect to posterior circulation disease, the true positive and true negative rates were 100% and 50%, respectively. Regarding identification of dual circulation disease, the true positive and true negative rates were 71% and 82%, respectively.


Regional cerebral blood velocity in infants. A real-time transcranial and fontanellar pulsed Doppler study.
To quantitate blood velocity while maintaining the real-time ultrasound image of the intracranial vessels in infants, we used a commercial phased-array pulsed Doppler scanner and developed a transcranial technique to measure the middle cerebral artery velocity, and a fontanellar approach to measure flow velocities in the basilar, internal carotid, anterior cerebral, and the pericallosal arteries. In 22 healthy term and 25 stable preterm infants, the peak spectral systolic velocities in the internal carotid and basilar arteries in term infants were 45 +/- 3.1, and 38.8 +/- 2.5 cm/sec, (mean +/- SEM), respectively. A hierarchical pattern of velocity variation was noted between the large and small intracranial vessels in both the term and preterm infants. The velocities were 30-40% higher in the proximal than in the smaller distal, anterior cerebral, and pericallosal arteries (P less than 0.05). Although the velocities in corresponding vessels were slightly lower in preterm infants than in the term, the differences were statistically not significant. In both groups, the end diastolic velocities did not change significantly among the large and small arteries; therefore, a significant variation in Pourcelot's index (PI, the ratio of maximum systolic-end diastolic difference to the systolic velocity) was noted between the internal carotid and the pericallosal arteries: 0.88 +/- 0.01 vs. 0.76 +/- 0.02, (P less than 0.05). A nearly parabolic velocity profile was documented in the vessels studied.


Assessment of risk perception and adoption of safety measures during Covid-19 pandemic in Pakistan: a survey study through mobile application.
This coronavirus disease's impact, effect, and spread largely depend on how people behave and react mindfully. According to the knowledge, attitude, and practices (KAP) theory, the only way to war against COVID-19 is to ensure allegiance to all Pakistanis' controlled maneuvers nationwide. To control this pandemic, the determination of safety measures practiced by people and their associated factors are of great importance. This study aimed to explore Pakistani's perception of the economic and psychological risks related to COVID-19 and the association of perceived risks with adopting safety measures. The was conducted among 1,058 Pakistanis using a self-developed survey questionnaire from March 15 to June 15, 2020 - using a mobile application. The analysis revealed that more participants agreed that (i) Covid 19 is associated with economic threats to the overall economy, (ii) social media and the Government is causing more psychological threat than the virus, and (iii) personal and imposed safety measures should be observed during the spread of the virus. Moreover, regression analysis indicates that economic and psychological threats were significantly and positively correlated with personal safety measures but not government-imposed safety measures. Moreover, economic and psychological threats are significant predictors of personal safety measures. This study is helpful as it is the first to inform about the threats associated with this pandemic and their association with safety measures practiced by Pakistan's population. The online version contains supplementary material available at 10.1007/s12652-022-04421-8.


Side reactions in peptide synthesis. V.A reexamination of the mixed anhydride method.
Acylation of amino acid beta-naphthylamides with protected (Boc) amino acidisobutylcarbonic acid mixed anhydrides resulted in each case in the formation of some undesired by-product: an isobutyloxycarbonylamino acid beta-naphthylamide. The amount of this second acylation product was particularly high, with the hindered amino acids valine and isoleucine as carboxyl-components. The nature of the amino component had no major influence on the extent of this side reaction.


A role for mRNA trafficking and localized translation in peroxisome biogenesis and function?
Peroxisomes are distinct membrane-enclosed organelles involved in the β-oxidation of fatty acids and synthesis of ether phospholipids (e.g. plasmalogens), as well as cholesterol and its derivatives (e.g. bile acids). Peroxisomes comprise a distinct and highly segregated subset of cellular proteins, including those of the peroxisome membrane and the interior matrix, and while the mechanisms of protein import into peroxisomes have been extensively studied, they are not fully understood. Here we will examine the potential role of RNA trafficking and localized translation on protein import into peroxisomes and its role in peroxisome biogenesis and function. Given that RNAs encoding peroxisome biogenesis (PEX) and matrix proteins have been found in association with the endoplasmic reticulum and peroxisomes, it suggests that localized translation may play a significant role in the import pathways of these different peroxisomal constituents.


[Identity of polystome larvae, parasites of Dicroglossus occipitalis tadpoles, on the Ivory Coast (author's transl)].
The morphological analysis of the haptorial hooklets of african Polystomatidae shows that many species of larvae parasitize the tadpoles of Dicroglossus occipitalis (Günther). These multiple infestations are in contrast to the close parasitic specificity recognized by the adult Polystomes. This difference is explained by the behaviour of the host and the notion of supplying host is introduced.


A genome-wide association study of chronic spontaneous urticaria risk and heterogeneity.
Chronic spontaneous urticaria (CSU) is a dermatologic condition characterized by spontaneous, pruritic hives and/or angioedema that persists for 6 weeks or longer with no identifiable trigger. Antihistamines and second-line therapies such as omalizumab are effective for some CSU patients, but others remain symptomatic, with significant impact on quality of life. This variable response to treatment and autoantibody levels across patients highlight clinically heterogeneous subgroups. We aimed to highlight pathways involved in CSU by investigating the genetics of CSU risk and subgroups. We performed a genome-wide association study (GWAS) of 679 CSU patients and 4446 controls and a GWAS of chronic urticaria (CU)-index, which measures IgG autoantibodies levels, by comparing 447 CU index-low to 183 CU index-high patients. We also tested whether polygenic scores for autoimmune-related disorders were associated with CSU risk and CU index. We identified 2 loci significantly associated with disease risk. The strongest association mapped to position 56 of HLA-DQA1 (P = 1.69 × 10-9), where the arginine residue was associated with increased risk (odds ratio = 1.64). The second association signal colocalized with expression-quantitative trait loci for ITPKB in whole blood (Pcolocalization = .997). The arginine residue at position 56 of HLA-DQA1 was also associated with increased risk of CU index-high (P = 6.15 × 10-5, odds ratio = 1.86), while the ITKPB association was not (P = .64). Polygenic scores for 3 autoimmune-related disorders (hypothyroidism, type 1 diabetes, and vitiligo) were associated with CSU risk and CU index (P < 2.34 × 10-3, odds ratio > 1.72). A GWAS of CSU identified 2 genome-wide significant loci, highlighting the shared genetics between CU index and autoimmune disorders.


Neuropilin-2 is a receptor for semaphorin IV: insight into the structural basis of receptor function and specificity.
Neuropilins bind secreted members of the semaphorin family of proteins. Neuropilin-1 is a receptor for Sema III. Here, we show that neuropilin-2 is a receptor for the secreted semaphorin Sema IV and acts selectively to mediate repulsive guidance events in discrete populations of neurons. neuropilin-2 and semaIV are expressed in strikingly complementary patterns during neurodevelopment. The extracellular complement-binding (CUB) and coagulation factor domains of neuropilin-2 confer specificity to the Sema IV repulsive response, and these domains of neuropilin-1 are necessary and sufficient for binding of the Sema III semaphorin (sema) domain. The coagulation factor domains alone are necessary and sufficient for binding of the Sema III immunoglobulin- (Ig-) basic domain and the unrelated ligand, vascular endothelial growth factor (VEGF). Lastly, neuropilin-1 can homomultimerize and form heteromultimers with neuropilin-2. These results provide insight into how interactions between neuropilins and secreted semaphorins function to coordinate repulsive axon guidance during neurodevelopment.


Comparative Analysis of the Effects of Escitalopram, Pramipexole, and Transcranial Magnetic Stimulation on Depression in Patients With Parkinson Disease: An Open-Label Randomized Controlled Trial.
This study aimed to compare the effects of different antidepressant therapies on depression in patients with Parkinson disease (PD) and to provide a reference for clinical treatment. A total of 328 patients with idiopathic PD were selected consecutively. Subjects met Diagnostic and Statistical Manual of Mental Disease , Fourth Edition , criteria for a depressive disorder, or operationally defined subsyndromal depression, and scored greater than 17 on the 17-item Hamilton Depression Scale (HAMD-17). One hundred thirty-one patients with PD accompanied with depression were enrolled into the experimental group. The subjects were randomly divided into 4 groups, and 118 were eventually completed: routine treatment group (n = 29), routine treatment + escitalopram group (n = 29), routine treatment + pramipexole group (n = 31), and routine treatment + transcranial magnetic stimulation (TMS) group (n = 29). After 4 weeks of treatments, the efficacy of each treatment was evaluated using HAMD score and reduction rate. After 4 weeks of treatment, the HAMD score was used for pair-to-pair comparison between the 4 groups. The therapeutic efficiency of escitalopram, pramipexole, and repetitive TMS was superior to routine anti-PD treatment, and the differences were statistically significant ( P < 0.05). There was no statistical difference between escitalopram and pramipexole, but all of them were superior to rTMS. Further logistic regression analysis suggested that 50% reduction in HAMD score from baseline was associated with the treatment method. Among them, escitalopram had statistical significance ( P < 0.05). Escitalopram, pramipexole, and high-frequency TMS had better efficacy in patients with PD complicated with depression. At 4 weeks, escitalopram showed better antidepressant effects and improved patients' quality of life and did not worsen motor function.


Safe Surgery During the COVID-19 Pandemic.
Coronavirus Disease-2019 (COVID-19) has had an enormous impact on all aspects of healthcare, but its effect on patients needing surgery and surgeons has been disproportionate. In this review, we aim to understand the impact of the pandemic on surgical patients and teams. We compiled the emerging data on pre-operative screening methods, vaccinations, safe-surgery pathways and surgical techniques and make recommendations for evidence-based safe-surgical pathways. We also present surgical outcomes for emergency, oncological and benign surgery in the context of the pandemic. Finally, we attempt to address the impact of the pandemic on patients, staff and surgical training and provide perspectives for the future. Surgical teams have developed consensus guidelines and established research priorities and safety precautions for surgery during the COVID-19 pandemic. Evidence supports that surgery in patients with a peri-operative SARS-CoV-2 infection carries substantial risks, but risk mitigation strategies are effective at reducing harm to staff and patients. Surgery has increased risk for patients and staff, but this can be mitigated effectively, especially for elective surgery. Elective surgery can be safely performed during the COVID-19 pandemic employing the strategies discussed in this review.


Cortical visual areas of the cat project differentially onto the nuclei of the accessory optic system.
Cortical projections to the nuclei of the cat's accessory optic system were demonstrated by anterograde transport and degeneration methods. Areas 21a, 21b, AMLS and PMLS were found to project to the medial, lateral and dorsal terminal accessory optic nuclei. Selective projections from area PLLS to the lateral terminal nucleus and from areas 17 and 18 to the medial terminal nucleus were noted. No terminal labeling was detected following injections of areas ALLS, DLS, 20a, 20b, 19, 7 or the splenial visual area. The accessory optic system has been implicated in the control of optokinetic nystagmus. Additional evidence supports a role for ipsilateral visual cortical projections in mediating optokinetic pursuit in the naso-temporal direction under monocular conditions. Thus the visual cortical projections we describe may partially underlie the observed functional laterality of monocularly elicited optokinetic pursuit in the cat. The present results further indicate that suprasylvian areas AMLS, PMLS and 21 are the cortical regions primarily responsible for descending visual influences on the cat's accessory optic nuclei.


Limited mediastinal lymph node dissection for non-small cell lung cancer according to intraoperative histologic examinations.
Although radioisotopic procedures are commonly used to detect sentinel lymph nodes in breast cancer surgery, these procedures are often problematic and not necessarily suitable for lung cancer surgery. Our previous study revealed that the mediastinal sentinel lymph node, defined as the regional mediastinal lymph node, consisted of nodes 2, 3, or 4 in right upper lobe cancers; 3, 7, or 8 in right lower lobe cancers; 4, 5, or 7 in left upper lobe cancers; and 4, 7, or 8 in left lower lobe cancers. On the basis of these findings, we pathologically investigated one representative lymph node at each of the 3 levels dissected during surgical intervention in 69 patients with non-small cell lung cancer from September 1993 through December 2002. Fifty-eight patients with lung cancer underwent lobectomies with limited mediastinal lymph node dissection according to this strategy. Mediastinal lymph node recurrence was observed in only one patient during 41 +/- 25 months (maximum, 98 months) of follow-up. The cancer-specific 5-year survivals were 96.6% in patients with pathologic stage IA disease (n = 31) and 67.4% in patients with stage IB disease (n = 16). These results suggested that limited mediastinal lymph node dissection is applicable to patients with non-small cell lung cancer whose regional mediastinal lymph nodes are not metastatic.


Oxidative stress and anti-oxidant responses to regular resistance training in young and older adult women.
The aging process is associated with increased production of free radicals, but regular exercise training might create a balance between oxidative stress and the anti-oxidant system. The aim of the present study was to investigate the effect of resistance training (RT) on the serum levels of tumor necrosis factor-α, malondialdehyde, total anti-oxidant capacity and nuclear factor-κB in young and older adult women. A total of 44 women were divided into four groups: older-training, older-control, young-training and young-control. The experimental groups carried out 12 weeks of RT with an intensity of 75% one repetition maximum. After finishing the RT program, total anti-oxidant capacity and nuclear factor-κB in both the young and older adult training groups were significantly increased, whereas malondialdehyde in the young and the older exercising groups decreased. In addition, malondialdehyde in both the older and young groups, and total anti-oxidant capacity in only the young group, were respectively lower and higher compared with their inactive counterparts. No significant changes in tumor necrosis factor-α occurred in training groups after the 12-week intervention, but the older and younger training groups had a significant difference with the young control group in the post-test. It seems that the strengthening of the anti-oxidant system resulting from regular RT in older adults is similar to those of young people. Geriatr Gerontol Int 2019; 19: 419-422.


Microsomal mediated metabolism of dialkylaryltriazenes. II. Isolation and identification of metabolites of 3,3-dimethyl-1-phenyltriazene.
After incubating 3,3-dimethyl-1-phenyltriazene with rat liver microsomes, acetanilid and derivatives of aniline and possibly of 3-methyl-1-phenyltriazene were found as metabolites and identified by mass spectrometry. This is the first time that directly formed metabolites (other than formaldehyde) of a dialkyltriazene were identified. The isolation of a derivative of 3-methyl-1-phenyltriazene as 3-acetyl-3-methyl-1-phenyltriazene supports other evidence that the triazenes are enzymically demethylated. Indication for the formation of phenylhydrazine was also obtained. In addition, hydrolysates of the polar fractions of the incubation mixture contained aniline and 4-hydroxy-aniline as a aglycones.


The use of poloxamer hydrogels for the assessment of biofilm susceptibility towards biocide treatments.
Poloxamer F127 is a non-toxic, di-block copolymer of polyoxyethylene and polyoxypropylene. Aqueous solutions (30% w/v) show thermoreversible gelation, being liquid at temperatures < 15 degrees C and robust gels at temperatures > 15 degrees C. Chilled poloxamer (30% in tryptone soya broth) was mixed with an inoculum of Pseudomonas aeruginosa (10(4) cfu ml-1) and placed as 100 microliters drops onto separate glass cover-slips. These were placed into sealed Petri dishes containing moistened cotton wool and incubated at 35 degrees C. Viable counts could be performed on the poloxamer gels by transfer of the coverslips to diluents at < 15 degrees C. Growth curves in the gels and in liquid batch cultures were indistinguishable from one another with stationary phase cell densities, being approximately 5 x 10(10) cfu ml-1 in each at 16 h. SDS-PAGE of cell envelope preparations showed the poloxamer-grown cells to exhibit a biofilm rather than planktonic phenotype. Susceptibility towards various concentrations of chlorhexidine, iodine and hydrogen peroxide was assessed for 10 min at 35 degrees C for suspensions of broth-grown cells and for incubated poloxamer-gels (1 and 16 h). The gels were immersed in biocide, on their glass supports, before transfer to neutralizer at 10 degrees C where dissolution was complete within 5 min. Further serial dilutions and plate counts were made. While modest decreases in susceptibility towards all biocides were associated with incorporation of the inoculum with the gel (1 h incubation), substantial changes were noted after prolonged incubation and adaptation to a biofilm phenotype (16 h incubation). The gel populations mimic the localized high cell densities observed in biofilms and will also be subject to the same nutrient and chemical gradients as found within natural biofilms. Thermoreversible gelation enables complete recovery of the test inoculum without further trauma. They therefore provide an effective model for assessing biofilm susceptibility towards biocides and would be suitable for screening programmes.


From dissection of disease pathogenesis to elucidation of mechanisms of targeted therapies: leukemia research in the genomic era.
Leukemia is a group of heterozygous diseases of hematopoietic stem/progenitor cells that involves dynamic change in the genome. Dissection of genetic abnormalities critical to leukemia initiation provides insights into the elusive leukemogenesis, identifies distinct subsets of leukemia and predicts prognosis individually, and can also provide rational therapeutic targets for curative approaches. The past three decades have seen tremendous advances in the analysis of genotype-phenotype connection of leukemia, and in the identification of molecular biomarkers for leukemia subtypes. Intriguingly, differentiation therapy, targeted therapy and chemotherapy have turned several subtypes of leukemia from highly fatal to highly curable. The use of all-trans retinoic acid and arsenic trioxide, which trigger degradation of PML-RARalpha, the causative fusion protein generated by t (15;17) translocation in acute promyelocytic leukemia (APL), has led to a dramatic improvement of APL clinical outcome. Imatinib mesylate/ Gleevec/STI571, which inhibits the tyrosine kinase activity of BCR-ABL oncoprotein, has now become the new gold standard for the treatment of chronic myeloid leukemia. Optimal use of chemotherapeutic agents together with a stringent application of prognostic factors for risk-directed therapy in clinical trials has resulted in a steady improvement in the treatment outcome of acute lymphoblastic leukemia. Hence, the pace of progress extrapolates to a prediction of leukemia control in the twenty-first century.


The molecular and epidemiological characteristics of carbapenemase-producing Enterobacteriaceae isolated from children in Shanghai, China, 2016-2021.
We isolated the carbapenemase-producing Enterobacteriaceae (CPE) strains from children during 2016-2021 in Shanghai, China and investigated the antimicrobial resistance, molecular and epidemiological features of these isolates. Antimicrobial susceptibility tests were performed to confirm the carbapenem resistance. Carbapenemase production was assessed by the rapid phenotypic identification of five major carbapenemases (KPC, NDM, VIM, IMP, and OXA-48), which were further confirmed by PCR amplification and sequencing. Multilocus sequence typing (MLST) was conducted for phylogenetic analyses. A total of 320 CPE strains were collected from 2016 to 2021, consisting of carbapenemase-producing Klebsiella pneumoniae (CP-Kpn, 55.0%), Escherichia coli (CP-Eco, 24.5%) and Enterobacter cloacae (CP-Ecl, 20.4%) and others (2, 0.1%). NDM was the primary carbapenemase (67.6%) in children, followed by KPC(26.4%), IMP(5.3%) and OXA-48 (0.6%). The minimum inhibitory concentration (MIC) for imipenem has been increasing from 2016 to 2021. NDM and KPC isolates are high resistant while IMP strains show the lower resistant to imipenem. Invasive infection accounted for 10.7% of CPE-related infections and was mainly caused by CP-Kpn (70.6%). NDM-Kpn was detected in 51.8% of infants (70.8% of neonates), while KPC-Kpn was mainly isolated from non-infants (56.3%∼64.3%). ST11 was the primary clone (64.6%) of KPC-Kpn and presented an increasing trend from 2016 to 2021. NDM is widely prevalent and transfers among CPE strains in children. NDM-Kpn shows the most serious threat to infants, especially to neonates. High-risk clone of ST11 KPC-Kpn should be paid more attention and monitored continuously in children.


Isoflurane anesthesia induces biphasic effect on dopamine release in the rat striatum.
The effect of isoflurane anesthesia on changes in the extracellular concentrations of dopamine (DA) and its metabolites (3-methoxytyramine (3-MT), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)) modulated by pargyline, monoamine oxidase inhibitor, was studied using in vivo microdialysis techniques. A microdialysis probe was implanted into the right striatum of male SD rats. Each rat (n=5-6) was given saline or the same volume of 30 or 75 mg kg(-1) pargyline intraperitoneally with or without 1 h isoflurane anesthesia (1 or 3%). Isoflurane anesthesia increased the extracellular concentration of DA in high dose (3%) and increased the metabolite concentrations in a dose-dependent manner. Pargyline administration increased the extracellular concentration of DA and 3-MT, and decreased that of other metabolites. After 30 mg kg(-1) pargyline treatment, 1% isoflurane-induced DA release and increasing of 3-MT were preserved, whereas high dose isoflurane (3%) decreased the concentration of metabolites (DOPAC and HVA), despite of the increase by low dose isoflurane (DOPAC). When 75 mg kg(-1) pargyline was administered, isoflurane anesthesia decreased the concentration of DA and DOPAC. The isoflurane-induced 3-MT increase was preserved in all experiments. Our results suggest that isoflurane anesthesia induced biphasic effect on DA regulation probably by the potentiation of DA release and the inhibition of DA synthesis. Isoflurane might modulate DA homeostasis presynaptically.


Eosinophilic myocarditis: Case report and brief review of the literature.
Eosinophilic myocarditis (EM) is a cardiac manifestation of hypereosinophilic syndrome with a high mortality rate. EM shares imaging features similar to other restrictive cardiopathies, and include patchy intramural late gadolinium enhancement on cardiac magnetic resonance with or without presence of biventricular thrombus. Diagnosis is confirmed on histopathology, and is the current gold standard. Here we report clinical presentation and imaging findings of EM in a 70-year-old woman who presented with fever and chills.


The treatment outcome and predictors of serological response in syphilis in a sexually transmitted infections center, China.
Serology is the mainstay for syphilis treatment monitoring. Baseline rapid plasma reagin (RPR) titre, HIV status, and syphilis stage have been found to be associated with the time to serological response among syphilis patients. This study mainly aims to evaluate the time to serological response, and to identify factors affecting the serological outcome. Medical records of syphilis cases diagnosed in Peking Union Medical College Hospital (PUMCH) between 2008 and 2018 were retrospectively reviewed. Kaplan-Meier analysis was performed to evaluate the median time to serologic response and cumulative probability of serologic response over time according to different variables. Cox regression model was conducted to find factors associated with serological response. There were 984 patients diagnosed with primary, secondary, or latent syphilis cases and receiving injections of benzathine penicillin G (BPG) as initial treatment at the Peking Union Medical College Hospital (PUMCH) between 2008 and 2018. Finally, data on 571 patients, including 49 (8.6%) primary syphilis, 261 (45.7%) secondary syphilis, and 261 (45.7%) latent syphilis, were used for analysis. It took longer time to achieve serological response for subjects aged ≥45 years than younger individuals (89 days versus 58 days; p=0.008). Males achieved serological response more quickly than females (71 days versus 83 days; p = 0.011). There was a significant difference in the time to serological response according to different syphilis stages (p < 0.001), with 55 days (95% CI, 43-67 days) for primary, 57 days (95% CI, 51-63 days) for secondary, and 117 days for latent syphilis. In addition, patients with lower baseline RPR titre had longer period to achieve serological response (252 days [95% CI, 129-375 days] for RPR titre ≤1:8, 78 days [95% CI, 63-93 days] for RPR titres from 1:16 to 1:32, and 53 days [95% CI, 49-57 days] for RPR titres ≥1:64, respectively; p<0.001). However, no significant difference in time to serological response to treatment was found according to HIV coinfection status. The result of multivariate Cox regression analysis showed that being older than 45 years with latent syphilis, HIV coinfection, or with baseline RPR titre ≤1:8 was associated with slow response. Among patients followed for at least 1 year or seroreverted, 128 (36.9%) had seroreverted within a year, and 219 (63.1%) still had a positive RPR after 1 year. For multiple logistical regression, being female and HIV coinfection were significantly associated with the failure of seroreversion (OR, 0.42 [95% CI, 0.26-0.68]; p <0.001). This study revealed that younger age, higher initial RPR titre, early syphilis stage, and HIV-negative status were associated with faster serological cure. Female sex, individuals with HIV coinfection, and latent syphilis were significantly associated with the failure of seroreversion.


Unilateral depletion of testicular glutathione levels in the rat following intratesticular injections of diethylmaleate and buthionine sulfoximine.
A method was developed to selectively deplete glutathione (GSH) in a single rat testis. Using intratesticular injections of a mixture of two GSH-depleting agents, diethylmaleate and buthionine sulfoximine, testicular GSH levels were decreased to 33-54% of control 2 hr after injection and remained suppressed for 24 hr. GSH levels in the contralateral testis and liver were not affected by this treatment. Comparisons between GSH-depleted and vehicle-injected (contralateral) testes, evaluated 2 weeks later, showed that although testis and epididymal weights and cauda epididymal sperm reserves were slightly reduced (to greater than or equal to 90% of controls), no changes were seen in testicular spermatid counts or in the morphology or motility of cauda epididymal sperm. An increase in histologically abnormal tubules localized to the injection site occurred in some GSH-depleted testes; however, the proportion of normal tubules containing step 19 spermatids was not affected. Thus, intratesticular injections of GSH-depleting agents selectively lowered GSH levels in the treated testis, with minimal adverse effects. This protocol can now be applied to investigate specific roles of GSH in the testes, particularly with regard to the possible modulation of the effects of testicular toxicants.


Chi-dependent DNA strand cleavage by RecBC enzyme.
Chi sites enhance in their vicinity homologous recombination by the E. coli RecBC pathway. We report here that RecBC enzyme catalyzes Chi-dependent cleavage of one DNA strand, that containing the Chi sequence 5'G-C-T-G-G-T-G-G3'. Chi-specific cleavage is greatly reduced by single base pair changes within the Chi sequence and by mutations within the E. coli recC gene, coding for a RecBC enzyme subunit. Although cleavage occurs preferentially with double-stranded DNA, the product of the reaction is single-stranded DNA. These results demonstrate the direct interaction of RecBC enzyme with Chi sites that was inferred from the genetic properties of Chi and recBC, and they support models of recombination in which Chi acts before the initiation of strand exchange.


Synergistic effects of EMPs and PMPs on pulmonary vascular leakage and lung injury after ischemia/reperfusion.
Vascular leakage is an important pathophysiological process of critical conditions such as shock and ischemia-reperfusion (I/R)-induced lung injury. Microparticles (MPs), including endothelial cell-derived microparticles (EMPs), platelet-derived microparticles (PMPs) and leukocyte-derived microparticles (LMPs), have been shown to participate in many diseases. Whether and which of these MPs take part in pulmonary vascular leakage and lung injury after I/R and whether these MPs have synergistic effect and the underlying mechanism are not known. Using hemorrhage/transfusion (Hemo/Trans) and aorta abdominalis occlusion-induced I/R rat models, the role of EMPs, PMPs and LMPs and the mechanisms in pulmonary vascular leakage and lung injury were observed. The concentrations of EMPs, PMPs and LMPs were significantly increased after I/R. Intravenous administration of EMPs and PMPs but not LMPs induced pulmonary vascular leakage and lung injury. Furthermore, EMPs induced pulmonary sequestration of platelets and promoted more PMPs production, and played a synergistic effect on pulmonary vascular leakage. MiR-1, miR-155 and miR-542 in EMPs, and miR-126 and miR-29 in PMPs, were significantly increased after hypoxia/reoxygenation (H/R). Of which, inhibition of miR-155 in EMPs and miR-126 in PMPs alleviated the detrimental effects of EMPs and PMPs on vascular barrier function and lung injury. Overexpression of miR-155 in EMPs down-regulated the expression of tight junction related proteins such as ZO-1 and claudin-5, while overexpression of miR-126 up-regulated the expression of caveolin-1 (Cav-1), the trans-cellular transportation related protein such as caveolin-1 (Cav-1). Inhibiting EMPs and PMPs production with blebbistatin (BLE) and amitriptyline (AMI) alleviated I/R induced pulmonary vascular leakage and lung injury. EMPs and PMPs contribute to the pulmonary vascular leakage and lung injury after I/R. EMPs mediate pulmonary sequestration of platelets, producing more PMPs to play synergistic effect. Mechanically, EMPs carrying miR-155 that down-regulates ZO-1 and claudin-5 and PMPs carrying miR-126 that up-regulates Cav-1, synergistically mediate pulmonary vascular leakage and lung injury after I/R. Video Abstract.


Stereoselective C-glycosylation reactions with arylzinc reagents.
A general, transition-metal-free, highly stereoselective cross-coupling reaction between glycosyl bromides and various arylzinc reagents leading to β-arylated glycosides is reported. The stereoselectivity of the reaction is explained by invoking anchimeric assistance via a bicyclic intermediate. Stereochemical probes confirm the participation of the 2-pivaloyloxy group. Finally, this new method was applied to a short and efficient stereoselective synthesis of Dapagliflozin and Canagliflozin.


The growth and metastasis of four commonly used tumour lines implanted into eight different sites: evidence for site and tumour effects.
The growth and metastasis of four commonly used experimental tumour lines have been compared after the implantation of cells into a lobe of the liver, the spleen, the left kidney, the peritoneal cavity, the thorax, the right thigh muscle, subcutaneously into the dorsolumbar region and intravenously into the tail vein or the right femoral vein. This was done to assess the importance of site in affecting metastatic distribution, and to determine whether any general conclusions could be drawn as to the role of this factor. Tumours grew at variable rates in different sites, but this did not affect the extent or distribution of metastasis. Each line gave a characteristic pattern that could be considerably modified by site. For example, in the spleen, metastasis was always extensively to the liver; in the kidney, and to some extent in the muscle, metastasis was similar to that obtained for intravenously injected cells; in the peritoneal cavity or thorax, metastasis was usually lower than from other sites; and in the liver, the metastasis to other lobes of the liver and to the lungs was modified. Many of these findings could be explained by both specific and non-specific factors operating at each site. It is suggested that interactions at the primary site of tumour growth may be very important in affecting metastasis, and that in the future more attention should be given to this factor in order to make progress in understanding tumour spread.


Mutagenicity of nitro- and amino-substituted carbazoles in Salmonella typhimurium. I. Monosubstituted derivatives of 9H-carbazole.
Mononitro, monoamino and monoacetamido carbazoles were assayed for mutagenicity in Salmonella typhimurium strains TA1535, TA1538, TA1537, TA1977, TA98 and TA100, with and without the addition of S9 from phenobarbital-induced rat liver. The role of bacterial metabolism of the nitro group was also studied using the additional strains TA98NR and TA98/1,8DNP6. None of the compounds was active in TA1535, while only 2-nitrocarbazole and 3-nitrocarbazole presented a weak mutagenicity towards its pKM101 derivative, TA100. All four nitrocarbazole isomers were mutagenic for TA1538 and TA98, their activities decreasing in the order: 2-nitrocarbazole approximately 3-nitrocarbazole > 1-nitrocarbazole > 4-nitrocarbazole. Direct-acting mutagenicities for TA1537 were lower than for TA1538, but varied in the same order. Nitro reduction was an important step of metabolic activation of nitrocarbazoles, as indicated by the dramatic reduction of activity with TA98NR, as compared to TA98. Results obtained with TA98/1,8DNP6 showed that O-acetyltransferase was only partly required for the expression of mutagenic potency of these compounds. 2-Aminocarbazole was a weak direct-acting mutagen for TA1538 and TA98. Its activity was strongly increased in the presence of S9 mix, while 3-aminocarbazole became active in these conditions. The acetamido derivatives were consistently less mutagenic than their parent amines. These results show that nitrocarbazoles and aminocarbazoles behave as reactive frameshift mutagens, acting mainly through the formation of esterified hydroxylamines. The very low activity of 4-nitrocarbazole might be related to an orientation of the nitro group perpendicular to the aromatic ring.


Cellulose, modified cellulose and synthetic membranes in the haemodialysis of patients with end-stage renal disease.
When the kidney fails the blood-borne metabolites of protein breakdown and water cannot be excreted. The principle of haemodialysis is that such substances can be removed when blood is passed over a semipermeable membrane. Natural membrane materials include cellulose or modified cellulose, more recently various synthetic membranes have been developed. Synthetic membranes are regarded as being more "biocompatible" in that they incite less of an immune response than cellulose-based membranes. To assess the effects of different haemodialysis membrane material in patients with end-stage renal disease (ESRD). We searched MEDLINE, EMBASE, PreMEDLINE, HealthStar CINAHL, the Cochrane Central Register of Controlled Trials (CENTRAL), Biosis, SIGLE, CRIB, UK National Research Register and reference lists of relevant articles. We contacted biomedical companies, known investigators and handsearched selected journals and conference proceedings. Date of most recent search: June 2004. All randomised controlled trials (RCTs) or quasi-RCTs comparing different haemodialysis membrane material in patients with ESRD. Two reviewers independently assessed the methodological quality of studies. Data was abstracted onto a standard form by one reviewer and checked by another. Relative Risk (RR) and weighted mean difference (WMD) with 95% confidence intervals (CI)) MAIN RESULTS: Thirty two studies were identified. Pre-dialysis ss(2) microglobulin concentrations were not significantly lower in patients treated with synthetic membranes (WMD -14.67, 95% CI -33.10 to 4.05). When analysed for change in ss(2) microglobulin, a fall was only noted with high-flux membranes. The incidence of amyloid was less in patients who were dialysed for six years with high-flux synthetic membranes (one study, RR 0.03, 95% CI 0.00 to 0.54). There was a significant difference in favour of the synthetic (high-flux) membrane in comparison to cellulose membranes for triglycerides (WMD -0.66; 95% CI -1.18 to -0.14) but not for modified cellulose membranes. Dialysis adequacy measured by Kt/V was marginally higher when cellulose membranes were used (WMD -0.10; 95% CI -0.16 to 0.04), whereas synthetic membranes achieved significantly higher Kt/V values when compared with modified cellulose membranes (WMD 0.20, 95% 0.11 to 0.29) . There were no data on quality of life measures. We found no evidence of benefit when synthetic membranes were compared with cellulose/modified cellulose membranes in terms of reduced mortality no reduction in dialysis-related adverse symptoms. Despite the relatively large number of RCTs undertaken in this area none of the included studies reported any measures of quality of life.


Histologic findings after gastrocystoplasty in rabbits.
The aim of this study was to investigate the long-term histologic changes after bladder augmentation with gastric segment in an animal subject. Gastrocystoplasty was performed in 13 young, 3-month-old male rabbits. Open biopsies were taken from the native bladder and the gastric segment preoperatively and at 3, 6, and 12 months postoperatively. Sections were examined with H&E and periodic acid-Schiff (PAS) staining. Indirect immune peroxidase method was additionally applied to detect the carcinoembrionic antigen, the proliferative activity, and the gene for the tumor protein p53 in the epithelium. On the native bladder, at the 3-month follow-up, polyps, mucosal edema, submucosal fibrosis, and squamous cell metaplasia were detected, which did not change during the follow-up. On the gastric segment, at the 3-month follow-up, parietal cell hyperplasia and inflammatory mucosal overgrowth were detected; at the 6-month follow-up, inflammation or atrophy of the gastric mucosa and colonic-type metaplasia was found. These alterations remained unchanged during later course of follow-up. Neither dysplasia nor malignancy was observed during the 12-month follow-up. The present study supports the clinical observations of low cancer risk after gastrocystoplasty and may indicate different effect of gastric secretion on uroepithelium and that of urine on gastric mucosa.


Medical Complexity among Children with Special Health Care Needs: A Two-Dimensional View.
To identify subgroups of U.S. children with special health care needs (CSHCN) and characterize key outcomes. Secondary analysis of 2009-2010 National Survey of CSHCN. Latent class analysis grouped individuals into substantively meaningful classes empirically derived from measures of pediatric medical complexity. Outcomes were compared among latent classes with weighted logistic or negative binomial regression. LCA identified four unique CSHCN subgroups: broad functional impairment (physical, cognitive, and mental health) with extensive health care (Class 1), broad functional impairment alone (Class 2), predominant physical impairment requiring family-delivered care (Class 3), and physical impairment alone (Class 4). CSHCN from Class 1 had the highest ED visit rates (IRR 3.3, p < .001) and hospitalization odds (AOR: 12.0, p < .001) and lowest odds of a medical home (AOR: 0.17, p < .001). CSHCN in Class 3, despite experiencing more shared decision making and medical home attributes, had more ED visits and missed school than CSHCN in Class 2 (p < .001); the latter, however, experienced more cost-related difficulties, care delays, and parents having to stop work (p < .001). Recognizing distinct impacts of cognitive and mental health impairments and health care delivery needs on CSHCN outcomes may better direct future intervention efforts.


Optimization of lipase-catalyzed transesterification of lard for biodiesel production using response surface methodology.
Biodiesel, an alternative diesel fuel made from renewable biological resources, has become more and more attractive recently. Combined use of two immobilized lipases with complementary position specificity instead of one lipase is a potential way to significantly reduce cost of lipase-catalyzed biodiesel production. In this study, the process of biodiesel production from lard catalyzed by the combined use of Novozym435 (non-specific) and Lipozyme TLIM (1,3-specific) was optimized by response surface methodology. The optimal reaction conditions were 0.04 of amount of lipase/oil (w/w), 0.49 of proportion of Novozym435/total lipases (w/w), 0.55 of quantity of tert-butanol/oil (v/v), 5.12 of quantity of methanol/oil (mol/mol), and 20 h of reaction time, by which 97.2% of methyl ester (ME) yield was attained, very close to the predicted value (97.6%). This optimal reaction condition could be true of other similar reactions with plant and animal oil resources; their ME yield could be higher than 95%. The lipases regenerated by washing with organic solvent after each reaction cycle could be continuously reused for 20 cycles without any loss of activity, exhibiting very high manipulation stability.


Ecotoxicity of pp'DDE to Daphnia magna.
pp'-Dichlorodiphenyl-dichloroethylene (pp'DDE), a metabolite of pp'-dichlorodiphenyl-trichloroethane poses a risk for many ecosystems in spite of the banning of the parent compound because of its persistence and bioaccumulability. Nevertheless, the knowledge of acute and chronic toxicity on aquatic organisms is still very poor. In the present study, Daphnia magna was exposed to varying concentrations of pp'DDE in water and through diet to determine both acute toxicity and potential for effects on reproduction and survivability. The 48 h IC50 was 5.08 μg L(-1) (3.76-7.01 μg L(-1)). As pp'DDE concentration in water was not stable and the amount assumed by food cannot be established with certainty, the results of chronic toxicity tests were expressed as the concentration in the organism which caused a negative effect. Grazing activity was affected with a pp'DDE concentration in the organism of 24 ng mg(-1) d.w., while the lowest observed effect concentration for fecundity reduction was 109 ng mg(-1) d.w.


Simplified Interpretation of the Erectile Function Domain of the International Index of Erectile Function.
This report describes a post hoc analysis of data from a randomized, double-blinded, placebo-controlled, flexible-dose, sildenafil trial in men with erectile dysfunction. To simplify interpretation of erectile function (EF) domain scores of the International Index of Erectile Function (IIEF). Men at least 18 years old with erectile dysfunction were randomized to receive sildenafil or placebo for 12 weeks. Men taking nitrates or nitric oxide donors were excluded. Responses for each IIEF EF domain question (questions 1-5 and 15) were combined into two broad categories ("success" for responses of the two most favorable categories of a question and "no success" for other responses). Each question was expressed in a logistic regression model (sildenafil and placebo groups combined) as a function of overall EF domain score. IIEF EF domain score and items. A four-point increase in the IIEF EF domain score was associated with an odds ratio of success of 6.1 for getting an erection, 29.2 for having a firm erection, 10.0 for able to penetrate,12.8 for maintaining erection, 4.0 for maintaining erection to completion, and 3.7 for erection confidence. An EF domain score of 22 was associated with a probability of success of 81% for getting an erection, 86% for having a firm erection, 89% for able to penetrate, 67% for maintaining an erection, 70% for maintaining an erection to completion, and 32% for erection confidence. For an EF domain score of 16, the corresponding probabilities of success were 22%, 4%, 20%, 4%, 22%, and 6%, respectively. These results provide stakeholders with a simplified and meaningful interpretation of IIEF EF domain scores based on six key aspects of EF.


Silicon and matrix macromolecules: new research opportunities for old diseases from analysis of potential mechanisms of breast implant toxicity.
An understanding of the normal and essential integration of the element silicon in biosystems, as well as knowledge of its fundamental chemistry, are crucial to understanding its role in health and disease. Modern organosilicon chemistry, based in part on the artificial silicon-carbon bond, coincided with the emergence of the biomaterials and bioengineering fields fifty years ago, and was thought to be a fortunate coincidence according to conventional wisdom that high-molecular-weight polymeric siloxanes were chemically and biologically inert. These concepts have been challenged by reports of silicone migration and degradation following insertion of gel-filled breast implants, claims of a novel systemic illness appearing in many breast implant recipients, and investigations implicating varied and permeating immunotoxic mechanisms of disease causation by breast devices. The present study develops additional potential pathogenetic ideas based on alterations of cell biochemistry by silicon-containing compounds, and offers correlation of the patients' diverse clinical features with plausable disruption of basic biological processes. This in turn raises new questions concerning everyday environmental exposure, has broad implications for multiple other diseases, can provide alternative directions for future investigative research, and may contribute to the ongoing redefinition of immune dysfunction and inflammation.


Pregnancy and childhood exposure to residential traffic noise and overweight at 7years of age.
Exposure to road traffic noise has been associated with adiposity and diabetes in adults. The suggested pathways have been through sleep disturbance and stress. Children may be particularly susceptible to noise induced sleep disturbance and stress and the effects hereof. To examine the association between traffic noise exposure during pregnancy and early childhood and adiposity in children. We identified 40,974 singletons from the Danish National Birth Cohort with parentally given questionnaire information on weight and height at 7-years of age. Road and railway traffic noise were modeled at all historical addresses and expressed as time-weighted means for two exposure periods (pregnancy and childhood). Adiposity was assessed using BMI z-scores and a dichotomous measure of childhood overweight based on age and sex specific cut-offs. Associations were analyzed using linear regression for BMI z-scores and logistic regression for risk of childhood overweight, adjusting for socioeconomic position, maternal BMI, maternal smoking, maternal age, parity and degree of urbanization. We found both pregnancy and childhood exposure to road traffic noise to be associated with a higher risk for childhood overweight (odds ratio (OR)=1.06 per 10dB, 95% confidence interval (CI): 1.00-1.12 for exposure during pregnancy and OR=1.06 per 10dB, 95% CI: 0.99-1.12 for childhood exposure). There were no associations between road traffic noise and BMI z-scores. We found no associations between railway noise and adiposity. We found suggestions of a positive association between road traffic noise and risk of overweight in 7-years old children.


16S rRNA gene sequencing reveals the effect of fluoxetine on gut microbiota in chronic unpredictable stress-induced depressive-like rats.
Gut microbiota is relevant to the pathogenesis of mental disorders including depression. This study aimed to investigate the influence of fluoxetine (FLX) on the gut microbiota in rats with Chronic Unpredictable Mild Stresses (CUMS)-induced depression. We confirmed that the 28-day CUMS-induced depression rat model. Chronic FLX administration weakly improved depressive-like behaviors in rats. Illumina 16S rRNA gene sequencing on rat feces showed CUMS increased the relative abundance of Firmicutes (60.31% vs. 48.09% in Control, p < 0.05) and Lactobacillus genus (21.06% vs. 6.82% in control, p < 0.05); FLX and CUMS increased Bacilli class (20.00% ~ 24.08% vs. 10.31% in control, p < 0.05). Collectively, our study showed that both CUMS and FLX changed the compositions of gut microbiota in rats. FLX and CUMS distinctly regulated the gut microbiota in depressed rats.


Mammary tumor immunoscintigraphy in rats: the use of 131I-anti-estriol 3-sulfate antibody.
The scintigraphic imaging of mammary tumors with anti-estriol 3-sulfate (E3 3-S) antibody was studied in rats. A chemical carcinogen, 7,12-dimethylbenz(a)anthracine (DMBA), induced mammary tumors in Sprague-Dawley female rats. Highly specific anti-E3 3-S antibody was prepared and radioiodinated by [131I]NaI using the chloramine-T method. At 24 h after administration of 131I-anti-E3 3-S antibody, goat anti-guinea pig immunogloblin G (IgG) was injected as the second antibody (SA) and nuclear scintigraphy was performed. Mammary tumors were clearly visualized following SA injection.


Hematopoietic colony-forming cell assays.
Hematopoiesis is the process by which stem cells divide and differentiate to produce the multiple types of mature cells found in blood. The process begins in early embryonic development and continues throughout adult life, primarily in the bone marrow. Various in vivo and in vitro assays have been developed to detect and assess stem cells and early multi-potential progenitors. While highly informative about primitive hematopoietic cells these assays are long and labour intensive. Alternatively, colony-forming cell (CFC) assays may be used to quantify more lineage-restricted progenitors in a simple in vitro assay. When cultured in a semi-solid medium containing the appropriate cytokines, CFCs are able to divide and differentiate into a colony of more mature cells that can be detected by light microscopy. This allows for the quantification of erythroid, myeloid, lymphoid, megakaryocytic, and multi-potential cell lineages from various cell sources. This chapter outlines the materials and methods used for the culture and assessment of CFC from humans, mice, and other species.


Retracted: A Meta-Analysis of CT as a Tool for Diagnosing and Treating Shoulder Joint Bankart Injuries.
[This retracts the article DOI: 10.1155/2022/9137706.].


Ubiquitin-specific peptidase 8 regulates the trafficking and stability of the human organic anion transporter 1.
Background Organic anion transporter 1 (OAT1) plays a vital role in avoiding the potential toxicity of various anionic drugs through the involvement of kidney elimination. We previously demonstrated that ubiquitin conjugation to OAT1 led to OAT1 internalization from cell surface, followed by degradation. Ubiquitination is a dynamic process, where deubiquitination is catalyzed by a class of ubiquitin-specific peptidases. Methods The role of ubiquitin-specific peptidase 8 (USP8) in hOAT1 function, expression and ubiquitination was assessed by conducting transporter uptake assay, biotinylation assay and ubiquitination assay. Results We demonstrated that USP8 overexpression in hOAT1-expressing cells led to an increased hOAT1 transporter activity and expression, which correlated well with a reduced hOAT1 ubiquitination. Such phenomenon was not observed in inactive USP8 mutant-transfected cells. In addition, the knockdown of endogenous USP8 by USP8-specific siRNA resulted in an increased hOAT1 ubiquitination, which correlated well with a decrease in hOAT1 expression and transport activity. Biotinylation experiments demonstrated that USP8-induced increase in hOAT1 expression and transport activity occurred through a deceleration of the rates of hOAT1 internalization and degradation. Conclusions These results indicated the regulatory role of USP8 in OAT1 function, expression, trafficking, and stability. General significance USP8 could be a new target for modulating OAT1-mediated drug transport.


Transoral Thyroidectomy: Safety and Outcomes of 200 Consecutive North American Cases.
North American adoption of the transoral endoscopic thyroidectomy vestibular approach (TOETVA) has been limited due to concerns regarding the generalizability of published outcomes, as data are predominantly from Asian cohorts with a different body habitus. We describe our experience with TOETVA in a North American population in the context of the conventional transcervical approach thyroidectomy (TCA). Cases of TOETVA and TCA were reviewed from August 2017 to March 2020 at a tertiary care center. Outcomes included operative time, major (permanent recurrent laryngeal nerve (RLN) injury, permanent hypoparathyroidism, hematoma, conversion to open surgery), and minor complications. The TOETVA cohort was stratified into body mass index (BMI) classes of underweight/normal < 25 kg/m2, overweight 25-29.9 kg/m2, and obese ≥ 30 kg/m2 for comparative analysis. Multivariable logistic regression analyses were performed for odds of cumulative complication. Two hundred TOETVA and 333 TCA cases were included. There was no difference in incidence of major complications between the TOETVA and TCA cohorts (1.5% vs. 2.1%, p = 0.75). No difference was found in the rate of temporary RLN injury (4.5% vs. 2.1%, p = 0.124) or temporary hypoparathyroidism (18.2% vs. 12.5%, p = 0.163) for TOETVA and TCA, respectively. Surgical technique (TOETVA vs TCA) did not alter the odds of cumulative complication (OR 0.69 95% CI [0.26-1.85]) on logistic regression analysis. In the TOETVA cohort, higher BMI did not lead to a significantly greater odds of cumulative complication, 0.52 (95% CI [0.17-1.58]) and 1.69 (95% CI [0.74-3.88]) for the overweight and obese groups, respectively. TOETVA can be performed in a North American patient population without a difference in odds of complication compared to TCA. Higher BMI is not associated with greater likelihood of complication with TOETVA.


Ubiquitin-Proteasome System in ABA Signaling: From Perception to Action.
Protein post-translational modification (PTM) by ubiquitination has been observed during many aspects of plant growth, development, and stress responses. The ubiquitin-proteasome system precisely regulates phytohormone signaling by affecting protein activity, localization, assembly, and interaction ability. Abscisic acid (ABA) is a major phytohormone, and plays important roles in plants under normal or stressed growth conditions. The ABA signaling pathway is composed of phosphatases, kinases, transcription factors, and membrane ion channels. It has been reported that multiple ABA signaling transducers are subjected to the regulations by ubiquitination. In particular, recent studies have identified different types of E3 ligases that mediate ubiquitination of ABA receptors in different cell compartments. This review focuses on modulation of these components by monoubiquitination or polyubiquitination that occurs in the plasma membrane, endomembranes, and from the cytosol to the nucleus; this implies the existence of retrograde and trafficking processes that are regulated by ubiquitination in ABA signaling. A number of single-unit E3 ligases, components of multi-subunit E3 ligases, E2s, and specific subunits of the 26S proteasome involved in ABA signal regulation are discussed. Dissecting the precise functions of ubiquitination in the ABA pathway may help us understand key factors in the signaling of other phytohormones regulated by ubiquitination and other types of PTMs.


Expression level of BTN3A1 on the surface of CD14+ monocytes is a potential predictor of γδ T cell expansion efficiency.
Human γδ T cells expressing Vγ9Vδ2 T cell receptors exert a robust response to pathogens and malignant cells. These cells are activated by BTN3A1, which is expressed by pathogen-derived phosphoantigens (pAgs) or host-derived pAgs that accumulate in transformed cells or in cells exposed to aminobisphosphonates. Activated Vδ2 (+) T cells exert multiple effector functions; therefore, they are a promising candidate for immunotherapy. However, not all donors have γδ T cells with adequate proliferative activity. Here, we performed ex vivo culture of γδ T cells from 20 healthy donors and explored factors that may affect their expansion efficiency. Consistent with previous studies, we found that amplification of γδ T cells requires CD14+ monocytes to act as accessory cells. We also show here that surface expression of BTN3A1 by monocytes correlates positively with γδ T cell expansion. Moreover, treatment with BTN3A1-Fc increased the expansion efficiency of peripheral blood mononuclear cells (PBMCs) from donors harboring γδ T cells with poor expansion capacity. Taken together, the data suggest that the level of BTN3A1 expressed on the surface of monocytes is a useful biomarker for predicting the degree of expansion of γδ T cells.


Increased esophageal mucosal/submucosal blood flow in patients with gastroesophageal reflux disease: normalization by treatment with a proton pump inhibitor.
Mucosal injury caused by gastroesophageal reflux may result in changes in esophageal mucosal blood flow. Little is known about esophageal mucosal blood flow in patients with gastroesophageal reflux disease (GERD). Here we examined esophageal mucosal blood flow and the effects of treatment in patients with GERD. The subjects included 41 cases (21 males and 20 females, mean age 64.2 years) in whom endoscopy was warranted in patients complaining of heartburn and/or regurgitation. We also studied six normal control subjects. Patients underwent endoscopy, laser Doppler flow meter measurements, and endoscopic ultrasonography before and after treatment. Esophageal mucosal/submucosal blood flow was increased in patients with GERD compared with the control patients. The thickness of the whole esophageal wall and that of the mucosal and submucosal layers of the esophagus correlated significantly with esophageal mucosal/submucosal blood flow. The increased esophageal mucosal/submucosal blood flow significantly decreased after 4 weeks' treatment with lansoprazole, a proton pump inhibitor. Our results indicated that the pathophysiology or underlying mechanisms of GERD includes increased esophageal mucosal/submucosal blood flow, which correlates with the thickness of the esophageal wall, but is reversible and responds to treatment with lansoprazole. This suggests that proton pump inhibitors can effectively treat GERD and promote histological normalization of the mucosa and submucosa in the lower esophagus.


NRF2 modulation in TRAMP mice: an in vivo model of prostate cancer.
Prostate cancer (PCa) is one of the most common cancers worldwide and oxidative stress is involved in its occurrence, development and progression. In fact, in transgenic adenocarcinoma of mouse prostate (TRAMP) mice, prostate cancer onset is associated with the methylation of the first five CpG in the nuclear factor erythroid 2-related factor 2 (NRF2) promoter, a key regulator of oxidative stress response, leading to its downregulation and accumulation of reactive oxygen species (ROS). It has been demonstrated that both natural and synthetic compounds can reactivate NRF2 expression inhibiting the methylation status of its promoter by downregulation of DNA methyltransferases (DNMTs) and histone deacetylases (HDACs). Interestingly, NRF2 re-expression significantly reduced prostate cancer onset in TRAMP mice highlighting an important role of NRF2 in prostate tumorigenesis. We analysed the current literature regarding the role of natural and synthetic compounds in modulating NRF2 pathway in TRAMP mice, an in vivo model of prostate cancer, to give an overview on prostate carcinogenesis and its possible prevention. We can conclude that specific natural and synthetic compounds can downregulate DNMTs and/or HDACs inhibiting the methylation status of NRF2 promoter, then reactivating the expression of NRF2 protecting normal prostatic cells from ROS damage and tumorigenesis.


Role of CD8+ and WC-1+ gamma/delta T cells in resistance to Mycobacterium bovis infection in the SCID-bo mouse.
The role of various effector T cell populations in the bovine immune response to Mycobacterium bovis infection is poorly understood. This is largely due to the difficulties associated with performing in vivo challenge studies in the natural host species. In this report, we utilized a fetal bovine-severe combined immunodeficient (SCID-bo) xenochimeric mouse model to study the protective role of two putative effector cell types, CD8+ T cells and a subpopulation of gamma/delta T cells that express WC-1, a member of the cysteine-rich scavenger receptor superfamily (CRSR). We demonstrate that CD8+ T cells play a key role in protection and contribute substantially to bovine IFN-gamma mRNA levels at 30 days post-infection. The role of WC-1 bearing cells to protection was less definitive but our results suggest that this population may play a pivotal role early in infection. Granuloma architecture was altered in anti-WC-1 (ILA29) but not anti-CD8 (ILA51) -treated animals, suggesting that this population may be involved in recruitment of various cell types to sites of infection.


Postpartum aggression in rats does not influence threshold currents for EBS-induced aggression.
Female Wistar rats were tested for aggressive behaviour induced by electrical brain stimulation (EBS) in the lateral hypothalamus. Threshold currents for the induction of aggression were determined on several days before the females were paired with experienced breeder males. Beginning in the second week of pregnancy threshold current values were measured once or twice weekly. No change in thresholds was observed either during pregnancy, the early postpartum period or after weaning. Lactation was the only period during which the females were spontaneously aggressive towards male intruders in their home cage, but not in the EBS cage. Analysis of bite targets revealed no difference between the bite patterns in the postpartum maternal aggression test and the EBS-induced attacks. The results demonstrate that the change in physiological and hormonal status in pregnant and lactating females has no influence on the propensity to attack during EBS. The similarity in wound patterns does not advocate a major difference in the types of aggression studied. We speculate upon the nature of EBS-induced attacks as the activation of a rigid, final pathway of aggression which is rather insensitive to mild modulations.


Characterization of in vitro oxidized barstar.
The polypeptide inhibitor of the ribonuclease barnase, barstar, has two cysteine residues in positions 40 and 82. These have been proposed to form a disulfide bridge leading to an increase in stability without changing the inhibitory activity of the protein. Barstar and a mutant (E80A) were oxidized in vitro and the biochemical and physico-chemical properties of the oxidized monomers were analysed. The oxidized proteins show no inhibition of barnase using a plate assay and are significantly destabilized. CD spectra indicate a loss of secondary structure. The amino acid substitution E80 --> A stabilizes the oxidized barstar to about the same extent as it does the reduced protein, indicating, however, that the helical region which it is in is intact.


Smoking status: A tacit screen for postpartum depression in primary care settings.
Universal screening for postpartum depression (PPD) remains an unachieved national priority. A tacit screen that requires no additional resources for administration can help to achieve this priority. We examine the predictive utility of using smoking as a tacit screen for PDD. We first establish smoking is a valid proxy for more prominent psychosocial determinants of PPD and is a predictor for PPD. We analyzed PRAMS data (2012-2015; N=134,435). Time of smoking was categorized as nonsmoker, during the prenatal period, the postpartum, or continuously; PPD was assessed using two PHQ-2 style questions. Compared to nonsmokers, women who smoked only during the prenatal period (OR: 1.41; 95% CI: 1.06 - 1.86), only during the postpartum (OR: 1.33; 95% CI: 1.18 - 1.49), and continuously throughout both periods (OR: 1.54; 95% CI: 1.41 - 1.69) were more likely to experience PPD. Smoking assessed at a prenatal visit (SN: 0.90, SP: 0.21), postpartum visit (SN: 0.86, SP: 0.25), or assessed at both visits (SN: 0.90, SP: 0.19) performed relatively well as a tacit screen for PPD, performing better among unmarried women (SN: 0.75 - 0.81; SP: 0.29 - 0.36). In this study, the criterion of positivity used was PRAMS' adapted version of the PHQ-2. This tacit screen may perform differently relative to a clinical diagnosis. Time of smoking predicts risk of PPD and can be used to tacitly screen for PPD with reasonable accuracy without requiring any additional time in settings with limited resources for routine screening of PPD.


Characterizing the gut microbiome of broilers raised under conventional and no antibiotics ever practices.
Meat from broilers raised without the use of antibiotics is becoming increasingly popular among consumers. Consequently, interest in the microbial profiling of chickens produced under nonconventional practices is growing, however, research on this topic is lacking. The current study was designed to characterize the dynamics of gut microbial populations of broilers raised under conventional and no antibiotics ever (NAE) practices. Four commercial farms (2 conventional and 2 NAE) were included in this study. On each farm, cecal (n = 224) and ileal (n = 224) contents were collected from birds at different stages during the grow out of a single flock and following transportation to the processing facility. Cecal microbiota was dominated by the genera Escherichia and Enterococcus upon hatching in both conventional and NAE flocks, shifting with time toward predominantly Faecalibacterium and Bacteroides. The composition of cecal microbial communities of NAE broilers was different than that of conventional chickens (P ≤ 0.05). Conventional broilers harbored a rich, but less diverse cecal microbiota than NAE, while the ileal microbiota was primarily populated with genera previously named Lactobacillus, which exhibited a higher abundance in NAE broilers (P ≤ 0.05). In both production systems, the microbiota followed a similar temporal succession that was more evident in the ceca. Transportation to the processing plant impacted the microbial composition of the ileum (P ≤ 0.05), characterized by an increase in the relative abundance of Psychrobacter. Finally, differential abundance analysis showed a positive correlation between Campylobacter and Enorma within the cecum microbiota, and a negative correlation with Salmonella.


Particles of photosystem 2 contain plantacyanin.
PS2 particles prepared from chloroplasts of three plant species were shown to contain the basic blue copper protein, plantacyanin, which may be extracted from the particles by concentrated saline solutions containing Triton X-100. Antibodies to plantacyanin were found to inhibit the photosynthetic oxygen evolution performed by the particles. Thus, evidences were obtained for participation of this protein in the oxygen-evolving activity of PS2 particles.


Multiscale evaluation of cellular adhesion alteration and cytoskeleton remodeling by magnetic bead twisting.
Cellular adhesion forces depend on local biological conditions meaning that adhesion characterization must be performed while preserving cellular integrity. We presently postulate that magnetic bead twisting provides an appropriate stress, i.e., basically a clamp, for assessment in living cells of both cellular adhesion and mechanical properties of the cytoskeleton. A global dissociation rate obeying a Bell-type model was used to determine the natural dissociation rate ([Formula: see text]) and a reference stress ([Formula: see text]). These adhesion parameters were determined in parallel to the mechanical properties for a variety of biological conditions in which either adhesion or cytoskeleton was selectively weakened or strengthened by changing successively ligand concentration, actin polymerization level (by treating with cytochalasin D), level of exerted stress (by increasing magnetic torque), and cell environment (by using rigid and soft 3D matrices). On the whole, this multiscale evaluation of the cellular and molecular responses to a controlled stress reveals an evolution which is consistent with stochastic multiple bond theories and with literature results obtained with other molecular techniques. Present results confirm the validity of the proposed bead-twisting approach for its capability to probe cellular and molecular responses in a variety of biological conditions.


Alteration in topological properties of brain functional network after 2-year high altitude exposure: A panel study.
High altitude (HA) exposure leads to cognitive impairment while the underlying mechanism is still unclear. Brain functional network is crucial for advanced functions, and its alteration is implicated in cognitive decline in multiple diseases. The aim of current study was to investigate the topological changes in HA-exposed brain functional network. Based on Shaanxi-Tibet immigrant cohort, neuropsychological tests and resting-state functional MRI were applied to evaluate the participants' cognitive function and functional connection (FC) changes, respectively. GRETNA toolbox was used to construct the brain functional network. The gray matter was parcellated into 116 anatomically defined regions according to Automated Anatomical Labeling atlas. Subsequently, the mean time series for each of the 116 regions were extracted and computed for Pearson's correlation coefficients. The relation matrix was further processed and seen as brain functional network. Correlation between functional network changes and neuropsychological results was also examined. The cognitive performance was impaired by HA exposure as indicated by neuropsychological test. HA exposure led to alterations of degree centrality and nodal efficiency in multiple brain regions. Moreover, two subnetworks were extracted in which the FCs significantly decreased after exposure. In addition, the alterations in FCs within above two subnetworks were significantly correlated with changes of memory and reaction time. Our results suggest that HA exposure modulates the topological property of functional network and FCs of some important regions, which may impair the attention, perception, memory, motion ignition, and modulation processes, finally decreasing cognitive performance in neuropsychological tests.


Study of resilience and environmental adversity in midlife health (STREAM).
The Jerusalem study of resilience and environmental adversity in midlife health (STREAM) was established to examine the prevalence of common mental and physical health issues in mid-adulthood in the inner city of Jerusalem, and to examine their association with lifespan psychosocial factors of vulnerability and resilience. Participants were 811 randomly selected individuals from 7000 individuals who were born and grew up in inner-Jerusalem. Participants were 34-44 years old during first wave of STREAM assessment. Initial telephone surveys took place in 2007-2008 and participants were followed-up for a second survey 1 year later. Upon funding, a new wave is planned for 2017-2018. Survey topics comprised common health problems (e.g., type 2 diabetes/migraine), health markers (e.g., BMI), and psychiatric vulnerabilities (e.g., anxiety, post-traumatic stress, depressive symptoms, psychosis). Other measures included socioeconomic status, creativity, life style behavior (e.g., smoking, exercise), social contact and adaptation to change. Survey data were retrospectively merged with data of national registry sources that included adverse psychosocial factors, psychiatric and social measures assessed across all developmental stages through midlife. This includes data available on birth factors, school achievement and adjustment, cognitive and behavioral functioning during young adulthood, psychiatric hospitalizations, immigration and socioeconomic status. Results on health outcomes of the first STREAM wave indicate that prevalence rates of health problems are comparable to recent World Mental Health Surveys. Apart from measures on adverse psychosocial factors, STREAM provides a cohort to examine resilience to developing health problems and having a poor health and functional outcome.


Synthesis and pharmacological activity of the stereoisomers of GP-88, a propafenone-type modulator of multidrug resistance.
All four stereoisomers of the propafenone-type MDR-modulator GP-88 (1) were synthesized using a combined approach with chiral pool building blocks and an acetalic protective group, which allows not only diastereoseparation but also assignment of absolute configuration via NMR spectroscopy. Those isomers with different configuration on the center of chirality in the propanolamine side chain showed statistically different PGP-inhibitory activity. Generally, the (R)-configured isomers were by a factor of nearby two higher active than the (S)-isomers. No differences in activity were observed for isomers with different configuration on the benzylic center of chirality.


Granular self-organizing map (grSOM) for structure identification.
This work presents a useful extension of Kohonen's Self-Organizing Map (KSOM) for structure identification in linguistic (fuzzy) system modeling applications. More specifically the granular SOM neural model is presented for inducing a distribution of nonparametric fuzzy interval numbers (FINs) from the data. A FIN can represent a local probability distribution function and/or a conventional fuzzy set; moreover, a FIN is interpreted as an information granule. Learning is based on a novel metric distance d(K)(.,.) between FINs. The metric d(K)(.,.) can be tuned nonlinearly by a mass function m(x), the latter attaches a weight of significance to a real number 'x' in a data dimension. Rigorous analysis is based on mathematical lattice theory. A grSOM can cope with ambiguity by processing linguistic (fuzzy) input data and/or intervals. This work presents a simple grSOM variant, namely greedy grSOM, for classification. A genetic algorithm (GA) introduces tunable nonlinearities during training. Extensive comparisons are shown with related work from the literature. The practical effectiveness of the greedy grSOM is demonstrated comparatively in three benchmark classification problems. Statistical evidence strongly suggests that the proposed techniques improve classification performance. In addition, the greedy grSOM induces descriptive decision-making knowledge (fuzzy rules) from the training data.


Extrastriatal SPECT-DAT uptake correlates with clinical and biological features of de novo Parkinson's disease.
Striatal dopamine transporter (DAT) uptake assessment through I123-Ioflupane Single-Pphoton Emission Computed Tomography (SPECT) provides valuable information about the dopaminergic denervation occurring in Parkinson's disease (PD). However, little is known about the clinical or biological relevance of extrastriatal DAT uptake in PD. Here, from the Parkinson's Progression Markers Initiative, we studied 623 participants (431 PD and 192 healthy controls) with available SPECT data. Even though striatal denervation was undoubtedly the imaging hallmark of PD, extrastriatal DAT uptake was also reduced in patients with PD. Topographically, widespread frontal but also temporal and posterior cortical regions showed lower DAT uptake in PD patients with respect to healthy controls. Importantly, a longitudinal voxelwise analysis confirmed an active one-year loss of extrastriatal DAT uptake within the PD group. Extrastriatal DAT uptake also correlated with the severity of motor symptoms, cognitive performance, and cerebrospinal fluid α-synuclein levels. In addition, we found an association between the Catechol-O-methyltransferase val158met genotype and extrastriatal DAT uptake. These results highlight the clinical and biological relevance of extrastriatal SPECT-DAT uptake in PD.


Apparent improvement in survival for carcinoma of the cervix following the introduction of chemoradiation--a Will Rogers phenomenon.
The improved survival for bulky cervical cancers (> 4cm) reported with combination platinum based chemoradiation (1999) prompted a move away from surgery as these cases frequently received adjuvant radiotherapy and were exposed to the morbidity of multimodality treatment. The period pre-1999 (Group 1) was compared with post-1999 (Group 2) when chemoradiation was the preferred treatment for bulky operable cervical cancer. Significantly more cases were treated surgically among Group 1 compared with Group 2 (79% vs. 62%; P < 0.001). Switching from surgery to radiotherapy improved survival in both treatment categories (73% vs. 78% and 37% vs. 44%, respectively) but with no improvement in overall survival (70%/ov.s 70%). Survival (86%) was similar in both groups among surgically treated women with tumors < 4 cm, but significantly more in Group 2 with negative nodes received postoperative adjuvant chemoradiotherapy (Groups 1 vs. 2; 16% vs.37.5%: P < 0.001) and overall the surgically treated patients received more not less multimodality treatment (46.5% vs. 59%; P = 0.7).


Dual infection of fetal and neonatal small ruminants with border disease virus and peste des petits ruminants virus (PPRV): neuronal tropism of PPRV as a novel finding.
Dual infection of 26 fetal and neonatal small ruminants with border disease virus (BDV) and peste des petits ruminants virus (PPRV) is reported. The animals included five aborted lamb fetuses, 19 neonatal lambs and two neonatal kids from flocks in regions of the Black Sea and the Aegean region. BDV and PPRV antigens were detected immunohistochemically in the brain, oral mucosa, intestine and lung of infected animals. Reverse transcriptase-polymerase chain reaction was used to demonstrate PPRV and BDV in samples of the spleen, lymph node, lung and brain from infected animals. On the basis of observations made, it is concluded that brain damage following intrauterine infection with BDV facilitates the passage of PPRV to the brain and results in infection of neuronal and glial cells by PPRV.


Follow our path with asparaginase activity: one technique, but different uses in clinical practice.
Acute lymphoblastic leukemia is the most common childhood malignancy. One of the drugs used in the treatment is Asparaginase, and monitoring of its activity levels enables better outcomes. Since 2018, our laboratory has been working to establish a regular analysis of activity. This implementation allowed to qualify care by detecting silent inactivation and also establishing desensitization as a safe way to overcome the lack of Erwinia. We were able to monitor children aged 0 to 18 years who were being treated with PEG-ASNase. The activity was assessed on days 7 (90 samples) and 14 (52 samples) after ASNase infusions. 142 samples were analyzed. 95.7% reached an adequate activity level (≥ 0.1 IU/mL). Patients treated with ASNase can develop allergic reactions. With the activity monitoring, is possible to circumvent situations like these and implement desensitization protocols for patients who had clinical hypersensitivity without inactivation. Desensitization induces temporary unresponsiveness to drug antigens, allowing the patients to proceed with the prescribed chemotherapy. We have received samples from four patients being treated with different desensitization protocols. Patients tolerated the protocols well. Only one had a grade 2 reaction during the infusion and activity < 0.1 IU/mL, which resulted in the switch to Erwinia. The dose adaptation is a possible and more recent use of ASNase monitoring and we were able to confirm the feasibility of PEG-ASNase desensitization protocols.


An event-related potential study on the time course of mental rotation in upper-limb amputees.
Mental rotation of body parts involves sequential cognitive processes, including visual processing, categorization and the mental rotation process itself. However, how these processes are affected by the amputation of a limb is still unclear. Twenty-five right upper-limb amputees and the same number of matched healthy controls participated in a hand mental rotation task. Thirty-two-channel electroencephalography (EEG) was recorded and the event-related potentials (ERPs) were analyzed. In the early visual processing phase, amputees and controls showed a similar P100. During the categorization phase, the amputees exhibited a decreased N200 compared with controls, and the decline was positively correlated with the time since amputation. In the mental rotation phase, controls had a larger ERP for the right upright hand than for the left upright hand, while amputees had a larger ERP for the left (intact) upright hand than for the right (affected) upright hand. Early visual processing was not affected by limb amputation. However, the perceptual salience of hand pictures decreased and the intact hand gained more significance in the amputees. Event-related potentials had the capability of showing the differences in categorization and mental rotation phases between amputees and controls.


Differences in air ambulance patient mix demonstrated by physiologic scoring.
Severity of illness or injury should be the primary justification for aeromedical transport. To determine whether differences in patient severity were detectable in air transport programs, helicopter-transported patients were examined by three established physiologic scores: the Trauma Score, the Acute Physiology and Chronic Health Evaluation Score, and the Rapid Acute Physiology Score. These scores were obtained prospectively on 1,868 consecutive patient transfer requests from six air medical services for periods ranging from two to six months. A patient meeting strict physiologic criteria was considered critically ill. Overall, 42.6% of the patients (range, 34.8% to 53.3%) were considered critically ill. Patients transported from inpatient hospital units and patients with cardiac disease were less likely to be critically ill than those transported emergently from scenes of accident or from emergency departments. There were also significant differences between programs with regard to the percentage of critically ill patients transported. This study suggests that physiologic scoring may be useful in comparing air ambulance programs and that a majority of patients transported by these services may not be critically ill.


New phylism theory and autism: pathognomonic impairment of troopbonding.
A phylism is a unit of existence, part of an individual's species heritage. It is neither nature nor nurture, but a phyletically dictated product of the interaction of both at a crucial developmental period which may be either prenatal, postnatal, or both. In the syndrome of autism, the phylism of troopbonding is specifically impaired, and other phylisms may be hypertrophic. The phylism of limerent (lover-lover) pairbonding is not impaired, and it may be the source of discordance with other members of the troop. Shyness is an attenuated manifestation of autism. The etiology of impaired troopbonding may be heritable, and almost certainly will prove to be neurochemical also, probably as an analogue of the Lesch-Nyhan syndrome. The lives of autistic children are subject to secondary shaping by the environment of living.


Protein Synthesis in the Developing Neocortex at Near-Atomic Resolution Reveals Ebp1-Mediated Neuronal Proteostasis at the 60S Tunnel Exit.
Protein synthesis must be finely tuned in the developing nervous system as the final essential step of gene expression. This study investigates the architecture of ribosomes from the neocortex during neurogenesis, revealing Ebp1 as a high-occupancy 60S peptide tunnel exit (TE) factor during protein synthesis at near-atomic resolution by cryoelectron microscopy (cryo-EM). Ribosome profiling demonstrated Ebp1-60S binding is highest during start codon initiation and N-terminal peptide elongation, regulating ribosome occupancy of these codons. Membrane-targeting domains emerging from the 60S tunnel, which recruit SRP/Sec61 to the shared binding site, displace Ebp1. Ebp1 is particularly abundant in the early-born neural stem cell (NSC) lineage and regulates neuronal morphology. Ebp1 especially impacts the synthesis of membrane-targeted cell adhesion molecules (CAMs), measured by pulsed stable isotope labeling by amino acids in cell culture (pSILAC)/bioorthogonal noncanonical amino acid tagging (BONCAT) mass spectrometry (MS). Therefore, Ebp1 is a central component of protein synthesis, and the ribosome TE is a focal point of gene expression control in the molecular specification of neuronal morphology during development.


Characteristics of cross-hybridization and cross-alignment of expression in pseudo-xenograft samples by RNA-Seq and microarrays.
Exploring stromal changes associated with tumor growth and development is a growing area of oncologic research. In order to study molecular changes in the stroma it is recommended to separate tumor tissue from stromal tissue. This is relevant to xenograft models where tumors can be small and difficult to separate from host tissue. We introduce a novel definition of cross-alignment/cross-hybridization to compare qualitatively the ability of high-throughput mRNA sequencing, RNA-Seq, and microarrays to detect tumor and stromal expression from mixed 'pseudo-xenograft' samples vis-à-vis genes and pathways in cross-alignment (RNA-Seq) and cross-hybridization (microarrays). Samples consisted of normal mouse lung and human breast cancer cells; these were combined in fixed proportions to create a titration series of 25% steps. Our definition identifies genes in a given species (human or mouse) with undetectable expression in same-species RNA but detectable expression in cross-species RNA. We demonstrate the comparative value of this method and discuss its potential contribution in cancer research. Our method can identify genes from either species that demonstrate cross-hybridization and/or cross-alignment properties. Surprisingly, the set of genes identified using a simpler and more common approach (using a 'pure' cross-species sample and calling all detected genes as 'crossers') is not a superset of the genes identified using our technique. The observed levels of cross-hybridization are relatively low: 5.3% of human genes detected in mouse, and 3.5% of mouse genes detected in human. Observed levels of cross-alignment are practically comparable to the levels of cross-hybridization: 6.5% of human genes detected in mouse, and 2.3% of mouse genes detected in human. We also observed a relatively high percentage of orthologs: 40.3% of cross-hybridizing genes, and 32.2% of cross-aligning genes.Normalizing the gene catalog to use Consensus Coding Sequence (CCDS) IDs (Genome Res 19:1316-1323, 2009), our results show that the observed levels of cross-hybridization are low: 2.7% of human CCDS IDs are detected in mouse, and 2.4% of mouse CCDS IDs are detected in human. Levels of cross-alignment using the RNA-Seq data are comparable for the mouse, 2.2% of mouse CCDS IDs detected in human, and 9.9% of human CCDS IDs detected in mouse. However, the lists of cross-aligning/cross-hybridizing genes contain many that are of specific interest to oncologic researchers. The conservative definition that we propose identifies genes in mouse whose expression can be attributed to human RNA, and vice versa, as well as revealing genes with cross-alignment/cross-hybridization properties which could not be identified using a simpler but more established approach. The overall percentage of genes affected by cross-hybridization/cross-alignment is small, but includes genes that are of interest to oncologic researchers. Which platform to use with mixed xenograft samples, microarrays or RNA-Seq, appears to be primarily a question of cost and whether the detection and measurement of expression of specific genes of interest are likely to be affected by cross-hybridization or cross-alignment.


Enhanced iron availability by protein glycation may explain higher infection rates in diabetics.
Serum proteins exist in a state of higher glycation among individuals with poor glycemic control, notably diabetics. These non-enzymatic modifications via the Maillard reaction have far reaching effects on metabolism and regulation, and may be responsible for increased infection rates within this population. Here we explore the effects of glycation on iron metabolism and innate immunity by investigating the interaction between siderophores and bovine serum albumin (BSA). Using a quartz crystal microbalance with dissipation monitoring to quantify association rates, glycated BSA exhibited a significantly reduced affinity for apo and holo enterobactin compared to a non-glycated BSA standard. Bacterial growth assays in the presence of BSA and under iron-limited conditions indicated the growth rate of enterobactin-producing E. coli increased significantly when the BSA was in a glycated form. The results, in addition to data in the literature, support the hypothesis that glycation of serum proteins may effectively increase the available free iron pool for bacteria in blood serum and weaken our innate immunity. This phenomenon may be partially responsible for higher infection rates in some diabetics, especially those with poor glycemic control.


Simultaneous (AC)n microsatellite polymorphism analysis and single-stranded conformation polymorphism screening is an efficient strategy for detecting ankyrin-1 mutations in dominant hereditary spherocytosis.
Nonsense/stop mutations in the ankyrin-1 gene (ANK1) are a major cause of dominant HS (dHS) (frequency of 23% in German dHS patients). To date, no common mutation has been found and therefore a simple mutation screening is not feasible. The reduced expression of one cDNA allele in the (AC)n microsatellite polymorphism of the ankyrin-1 gene, as seen in about 20% of Czech patients with dHS, may identify candidates with a possible frameshift/nonsense mutation. In order to verify the efficiency of this screening we screened the ankyrin-1 gene of 22 Czech dHS patients for both the reduced cDNA allele expression in the frequent (AC)n and the common exonic 26/39 polymorphisms, as well as for polymerase chain reaction (PCR) single-stranded conformation polymorphisms in any one of the 42 exons of ANK1. Anomalous PCR products were sequenced. We found seven new ANK1 frameshift/nonsense mutations in nine patients with, but in none of six patients without, a reduced cDNA allele expression (efficiency of 78%). We conclude that screening of dHS patients for such a reduced allele expression in common ANK1 polymorphisms is an efficient procedure for the identification of candidates for frameshift/nonsense mutations in the ankyrin-1 gene.


Oak decline analyzed using intraannual radial growth indices, δ(13)C series and climate data from a rural hemiboreal landscape in southwesternmost Finland.
Decline of pedunculate oak (Quercus robur L.) was studied in SW Finland. This is a region where the species is growing near its northern distributional limit globally and a recent decline of mature trees has been described regionally. Tree rings of declining oaks were compared to the chronologies of healthy and oaks that died, climate series and stable isotope discrimination of carbon (δ(13)C) of comparable mature trees. The radial growth (earlywood, latewood, and annual ring width) of declining oaks was clearly deteriorated in comparison to healthy oaks, but recuperated, compared to oaks that died, through all index types. Comparison of climate relationships between growth and δ(13)C, expected to reflect oaks' intrinsic water use efficiency, indicated enhancing resistance to droughts through the growing season. The growth and the climatic growth response was differentiated in declining oaks as compared with the healthy and oaks that died revealing that: (1) declining oaks exhibited decreasing competitive strength as indicated by reduced overall growth relative to healthy oaks, (2) the growth of declining oaks was more sensitive to winter conditions, but less restricted by summer droughts than the growth of other oaks, and (3) healthy oaks were seen having benefitted from the ongoing lengthening of the growing season. Lack of correlativity between growth and δ(13)C became evident as their responses to temperature and precipitation variations deviated drastically during the other but summer months. Our results indicate that several different ecological factors, rather than a single climatic factor (e.g., drought), are controlling the oak decline in the studied environment.


Plant-Based Family Food Packages and Weight Change in Children During the COVID-19 Pandemic.
Food insecurity and obesity coexist among children and families. We examined the association between receipt of plant-based family food packages from the Massachusetts General Hospital Revere Food Pantry and change in body mass index (BMI), adjusted for age and sex, among children during the COVID-19 pandemic. Among 35 children aged 2 to 18 years who received the packages between January 2021 and February 2022, we observed a change in BMI of -0.04 kg/m2 (95% CI, -0.08 kg/m2 to -0.01 kg/m2) for each package received. Our results suggest plant-based food packages might mitigate, and potentially reverse, BMI increase in children in households seeking food assistance.


The impact of precarious jobs on mental health: a gender-sensitive literature review.
The aim of this study is to analyse the extent to which research and knowledge production on a key occupational health issue-the impact of precarious employment on health-incorporates, and is sensitive to, a gender perspective. A systematic literature review was carried out to identify studies that analysed the relationship between precarious employment and mental health in the period January 2010-May 2018 through. A minimum of two independent reviewers assessed each article for quality and eligibility. A checklist was used to determine whether the articles included in the review incorporated a gender perspective. The search retrieved 1522 papers, of which 54 (corresponding to 53 studies) met the inclusion criteria. Of these 54 papers, 22 (40.7%) stratified the analyses by sex. Only 5.4% of the total of articles both stratified by sex and considered variables of household composition and marital status, while only 33.3% incorporated an intersectional perspective. None considered the distribution of domestic work and only a quarter (25.9%) approached the study and interpreted the results in terms of gender. Too few studies researching paid work and health include a gender perspective. This omission necessarily implies a biased interpretation of the reality of precarious employment and its impact on health.