Ultrasound evaluation of neck masses in children.
Neck masses in children are a frequent occurrence and in some instances create a diagnostic dilemma for the clinician. The authors' two-year experience using ultrasonography in the evaluation of 34 children with neck masses is reviewed. Twenty-two patients had lesions arising outside the thyroid gland; 12 lesions arose from the thyroid gland. Ultrasonography proved to be an accurate imaging modality for localizing the mass and demonstrating its relationship to the thyroid gland, trachea, and major neck vessels. The borders and extent of the lesions were well outlined, as well as their internal consistency. Based on this review, the authors recommend that ultrasonography be the first screening procedure in pediatric patients who present with perplexing neck masses.


Uropathogenic Escherichia coli endeavors: an insight into the characteristic features, resistance mechanism, and treatment choice.
Uropathogenic Escherichia coli (UPEC) are the strains diverted from the intestinal status and account mainly for uropathogenicity. This pathotype has gained specifications in structure and virulence to turn into a competent uropathogenic organism. Biofilm formation and antibiotic resistance play an important role in the organism's persistence in the urinary tract. Increased consumption of carbapenem prescribed for multidrug-resistant (MDR) and Extended-spectrum-beta lactamase (ESBL)-producing UPECs, has added to the expansion of resistance. The World Health Organization (WHO) and Centre for Disease Control (CDC) placed the Carbapenem-resistant Enterobacteriaceae (CRE) on their treatment priority lists. Understanding both patterns of pathogenicity, and multiple drug resistance may provide guidance for the rational use of anti-bacterial agents in the clinic. Developing an effective vaccine, adherence-inhibiting compounds, cranberry juice, and probiotics are non-antibiotical approaches proposed for the treatment of drug-resistant UTIs. We aimed to review the distinguishing characteristics, current therapeutic options and promising non-antibiotical approaches against ESBL-producing and CRE UPECs.


Assessment of midgut enteroendocrine peptide complement in the honey bee, Apis mellifera.
Peptides modulate physiological/behavioral control systems in all animals. In arthropods, midgut epithelial endocrine cells are one of the largest sources of these signaling agents. At present, little is known about the identity of the peptides that form arthropod midgut enteroendocrine peptidomes. While many techniques can be used for peptide structural identification, in silico transcriptome mining is one that has been used extensively for arthropod neuropeptidome prediction; this strategy has yet to be used for large-scale arthropod enteroendocrine peptide discovery. Here, a tissue-specific transcriptome was used to assess putative enteroendocrine peptide complement in the honey bee, Apis mellifera, midgut. Searches for transcripts encoding members of 42 peptide families were conducted, with evidence of expression for 15 groups found in the assembly: adipokinetic hormone, allatostatin A, allatostatin C, bursicon, CCHamide, CNMamide, diuretic hormone 31, diuretic hormone 44, insulin-like peptide, myosuppressin, neuropeptide F, pigment dispersing hormone, pyrokinin, short neuropeptide F, and tachykinin-related peptide. The proteins deduced from the midgut transcripts are identical in sequence, or nearly so, to those of Apis pre/preprohormones deposited previously into NCBI, providing increased confidence in the accuracy of the reported data. Seventy-five peptides were predicted from the deduced precursor proteins, 26 being members of known peptide families. Comparisons to previously published mass spectrometric data support the existence of many of the predicted Apis peptides. This study is the first prediction of an arthropod midgut peptidome using transcriptomics, and provides a powerful new resource for investigating enteroendocrine peptide signaling within/from the Apis midgut, a species of significant ecological/economic importance.


Brief Report: An Exploration of Alexithymia in Autistic and Nonautistic Transgender Adults.
Research has shown that many autistic people have alexithymia, a psychological trait characterized by difficulties in identifying and describing emotions. It is also now clear that there is a high rate of autism among transgender people, but we know little about the intersection of autism and gender diversity or about the clinical features of autistic transgender individuals. Seventy-eight nonautistic transgender, 56 autistic transgender, 106 nonautistic cisgender, and 107 autistic cisgender adults completed the Toronto Alexithymia Scale-20 and the Autism-spectrum Quotient as part of an online study. We also used the General Alexithymia Factor Score-8 as an additional alexithymia score. We found that nonautistic transgender participants reported significantly higher mean levels of alexithymia than nonautistic cisgender participants, and that there was a significant overrepresentation of individuals in this group who met the clinical cutoff for alexithymia. The difference in alexithymia between autistic cisgender and autistic transgender participants was nonsignificant, with >50% of each group scoring above the clinical cutoff point. Of note, when we used the General Alexithymia Factor Score-8, the difference between autistic transgender participants and autistic cisgender participants was significant, with autistic transgender participants reporting higher mean levels of alexithymia. Results suggest that nonautistic transgender individuals might be more prone to experience alexithymia (including at clinically significant levels) than nonautistic cisgender people. When autism occurs in transgender people, the average level and clinical rate of alexithymia is higher than among nonautistic transgender people and potentially higher than among autistic cisgender people. Our findings are in keeping with evidence of a subgroup of transgender people with "subclinical autism" and inconsistent with the notion that autism among transgender and gender diverse people is a "phenomimic" of autism. Lastly, our study highlights the potential importance of screening autistic and nonautistic transgender people for alexithymia.


Unexplained fetal baseline bradycardia in congenital panhypopituitarism.
An unexplained fetal baseline bradycardia apparently not secondary to uteroplacental insufficiency is reported. Congenital panhypopituitarism was diagnosed in the neonate. A common cause of both findings is speculated and a review of possible methods for antenatal diagnosis is given.


The minimal number of examined lymph nodes for accurate nodal staging and favorable prognosis in T1-2 supraglottic laryngeal squamous cell carcinoma.
The study aimed to investigate the minimal number of examined lymph nodes (ELNs) for accurate assessment of lymph node status and favorable prognosis in patients with stage T1-2 supraglottic laryngeal squamous cell carcinoma (LSCC) who received radical resection. Patients with stage T1-2 supraglottic LSCC from the Surveillance, Epidemiology, and End Results (SEER) database and the Chinese Academy of Medical Sciences, Cancer Hospital/National Cancer Center (NCC) were reviewed. The association of the ELN count with the identification of nodal metastasis and overall survival (OS) was analyzed using a multivariate regression model. Locally weighted scatterplot smoothing fitting curve and the 'changepoint' package were adopted to identify the optimal cut points using R. A total of 429 patients from the SEER database and 53 patients from NCC were enrolled. The probability of identifying nodal metastasis was positively related to the ELN count. For patients diagnosed with pathological stage N0 (pN0) disease, the mortality risks rapidly decreased when the amount of ELNs exceeded ten, and those with ELNs >10 had better OS. An adequate amount of ELNs benefits precise nodal staging in patients with stage T1-2 supraglottic LSCC. Ten lymph nodes are the minimum number of ELNs. For pN0 patients, an ELN count ≤10 is an unfavorable prognostic factor.


Cell death induced by a caspase-cleaved transmembrane fragment of the Alzheimer amyloid precursor protein.
The Alzheimer amyloid precursor protein (APP) is a transmembrane protein whose abnormal processing is associated with the pathogenesis of Alzheimer's disease. Activated caspases cleave APP and generate its carboxyl-terminally truncated fragment (APPdeltaC31). We have previously reported that overexpression of wild-type APP induces caspase-3 activation and apoptosis in postmitotic neurons. We now report that APPdeltaC31 potentially plays pathophysiological roles in neuronal death. Adenovirus-mediated overexpression of wild-type APP695 induced activation of caspase-3 and accumulation of APPdeltaC31 in postmitotic neurons derived from human NT2 embryonal carcinoma cells, whereas an APP mutant lacking the Abeta(1-20) region induced neither caspase-3 activation nor APPdeltaC31 generation. Inhibition of caspase-3 suppressed the generation of APPdeltaC31 in APP-overexpressing neurons. Forced expression of APPdeltaC31 induced apoptotic changes of neurons and non-neuronal cells, but failed to activate caspase-3. The cytotoxicity of APPdeltaC31 was also dependent on the Abeta(1-20) region. These results suggest that accumulation of wild-type APP activates neuronal caspase-3 to generate APPdeltaC31 that mediates caspase-3-independent cell death.


Toll-like receptor 3 L412F polymorphisms in infants with bronchiolitis and postbronchiolitis wheezing.
Innate immunity receptors play a critical role in host defense. In addition, the expression of Toll-like receptors (TLRs) has been connected to allergy and asthma. : To evaluate the association between the TLR3 L412F polymorphism and viral findings, clinical characteristics and subsequent wheezing in young infants with bronchiolitis. In all, 129 full-term infants hospitalized for bronchiolitis at age <6 months have been followed-up until the mean age of 1.5 years. Genotyping of the TLR3 L412F gene mutation was made by pyrosequencing. TLR3 L412F gene polymorphism including the minor allele T was overrepresented (52%) in infants hospitalized with bronchiolitis. The presence of the major allele C as homozygous was associated with repeated postbronchiolitis wheezing (7.06, 95% confidence interval 2.30-21.66). Preliminary evidence was found that TLR3 L412F gene polymorphism may be associated with bronchiolitis leading to hospitalization and postbronchiolitis wheezing.


Projections to the neostriatum from the cat precruciate cortex. Anatomy and physiology.
The projections to the striatum from two cytoarchitectonically and functionally distinct subdivisions of the cat precruciate motor cortex were studied using anatomical and electrophysiological techniques. Our results indicate that the medial precruciate cortex (stimulation of which leads to movements of the axial and proximal musculature) has a widespread projection to the lateral half of the caudate nucleus. The lateral precruciate cortex (stimulation of which leads to movements of the distal musculature) has a localized projection within the caudate nucleus adjacent to the internal capsule. Both medial and lateral precruciate areas project to the putamen. These results are discussed in relation to recent studies suggesting that the basal ganglia are involved in the enabling and sequencing of movements.


Nucleotide sequence of Citrus limon 26S rRNA gene and secondary structure model of its RNA.
The complete nucleotide sequence of Citrus limon 26S rDNA has been determined. The sequence has been aligned with large ribosomal RNA (L-rRNA) sequences of Escherichia coli, Saccharomyces cerevisiae and Oryza sativa. Nine extensive expansion segments in dicot 26S rRNA relative to E. coli 23S rRNA have been identified and compared with analogous segments of monocot, yeast, amphibian and human L-rRNAs. A secondary structure model for lemon 26S rRNA has been derived based on the refined model of E. coli 23S rRNA. It has been compared with other eukaryotic L-rRNAs models in terms of location of functionally important regions. Origin and evolution of L-rRNA expansion segments are discussed.


Incidence and predictors of initial antiretroviral therapy regimen change among children in public health facilities of Bahir Dar City, Northwest Ethiopia, 2021: multicenter retrospective follow-up study.
The inconsistent use of antiretroviral therapy can lead to the risk of cross-resistance between drugs. This reduces subsequent antiretroviral drug options. The burden of initial antiretroviral therapy ranges from 11.3% in South Africa to 71.8% in Malaysia. There is evidence that it is important to maintain children's initial antiretroviral therapy regimens. However, the incidence and predictive factors of initial antiretroviral therapy regimen changes in the research context are still unknown in the study setting. So, the study was aimed to assess incidence and predictors of initial antiretroviral therapy regimen changes among children in public health facilities of Bahir Dar city. A retrospective follow-up study was conducted in 485 children who received antiretroviral therapy between January 1, 2011 and December 30, 2020. These children were selected using simple random sampling techniques. The data were entered by Epi data 3.1 and the analysis was completed by STATA 14.0. The missing data was treated with multiple imputation method. The data were also summarized by median or mean, interquartile range or standard deviation, proportion and frequency. The survival time was determined using the Kaplan Meier curve. The Cox Proportional Hazard model was fitted to identify predictors of initial antiretroviral therapy regimen change. The global and Shoenfeld graphical proportional hazard tests were checked. Any statistical test was considered significant at P-value < 0.05. Finally, the data were presented in the form of tables, graphics and text. Among the 459 study participants, 315 of them underwent initial regimen changes during the study accumulation period. The shortest and longest follow up time of the study were 1 month and 118 months, respectively. The overall incidence rate of initial regimen change was 1.85, 95% CI (1.66-2.07) per 100 person-month observation and the median follow up time of 49 (IQR 45, 53) months. The independent predictors of initial regimen changes were poor adherence (AHR = 1.49, 95%CI [1.16, 1.92]), NVP based regimen (AHR = 1.45, 95%CI [1.15, 1.84]) comparing to EFV based regimen, LPVr based regimen (AHR = 0.22, 95%CI: (0.07, 0.70)) comparing to EFV based regimen, history of tuberculosis (AHR = 1.59, 95%CI [1.14, 2.23]) and being male (AHR = 1.28, 95%CI [1.02, 1.60]). In this study, the incidence of initial regimen change was high. The risk of initial regimen change would be increased by being male, poor adherence, having history of tuberculosis and NVP based initial regimen. Therefore, strengthening the health care providers' adherence counseling capability, strengthening tuberculosis screening and prevention strategies and care of initial regimen type choice needs attention in the HIV/AIDS care and treatment programs.


Effect of crucible wall roughness on the laminar/turbulent flow transition of the Ga75In25 alloy stirred by a rotating magnetic field.
The critical magnetic induction (Bcr) values of a melt flow produced by a rotating magnetic field (RMF), remaining laminar or turbulent, are essential in different solidification processes. In an earlier paper (Metall Res Technol 100: 1043-1061, 2003), we showed that Bcr depends on the crucible radius (R) and frequency of the magnetic field (f). The effect of wall roughness (WR) on Bcr was investigated in this study. Using ten different wall materials, we determined the angular frequency (ω) and Reynolds number (Re) as a function of the magnetic induction (B) and f using two different measuring methods (pressure compensation method, PCM; height measuring method, HMM). The experiments were performed at room temperature; therefore, the Ga75wt%In25wt% alloy was chosen for the experiments. Based on the measured and calculated results, a simple relationship was determined between Bcr and Re*, f, R, and WR, where the constants K1, K2, K3, and K4 depended on the physical properties of the melt and wall material:[Formula: see text].


Incorporating business courses into LIS programs in Hungary: An examination of ALA-accredited programs.
Libraries are currently undergoing drastic changes; these changes are a result of the proliferation of advanced technology, change in users' information-seeking behaviour and equally the diversity of information resources. As such, libraries and librarians are no longer enjoying the monopoly they used to enjoy as the sole providers of information. With the new changes, libraries are expected not only to be the custodians of information resources, but also facilitators of the same. This new role calls for libraries and librarians to have adequate skills and knowledge in a wide range of subjects that can enable them to survive the competitive environment. This study aims at establishing effective ways of incorporating business courses into LIS programmes in universities in Hungary as a strategy for enhancing economic development and sustainability in the country. The study used a literature review approach in analysing the implementation of business courses in Library and Information Sciences (LIS) programmes among the ALA (American Library Association) accredited programmes. The study established correlations between various ALA-accredited programmes that had incorporated business courses in their programmes. Using ALA-accredited programmes as a model, the study sought to analyse an appropriate model for restructuring LIS programmes in Hungary. From the findings, it was revealed that most ALA-accredited programmes had embraced various business courses in their programmes, although, it was noted that the majority of the programmes had business courses as electives. It was also observed that various titles of business courses amongst the ALA programmes were diverse and varied. From the analysis of this study, it was established that the incorporation of business courses in the LIS programme is beneficial, since most universities, globally, are trending towards the concept of entrepreneurial universities. However, there needs to be an appropriate strategy of ensuring that the courses chosen are market driven.


Effect of pituitary adenylate cyclase activating polypeptide 1-27 on ocular, cerebral and skin blood flow in humans.
The aim of the study was to assess the effects of a neuropeptide, pituitary adenylate cyclase activating polypeptide 1-27 (PACAP), on ocular, cerebral and skin blood flow in man. PACAP (0.01-10 pmol kg(-1) min(-1)) was administered intravenously to eight healthy male subjects in a placebo-controlled, double-blind dose escalation trial. Fundus pulsation amplitude was measured by laser interferometry, mean blood flow velocity in the ophthalmic artery and the middle cerebral artery measured by Doppler sonography, and regional blood flow of the skin was estimated by laser Doppler flowmetry. Infusion of PACAP at the highest dose of 10 pmol kg(-1) min(-1) induced a significant increase in fundus pulsation amplitude (+83.4%), mean flow velocity in the ophthalmic artery (+91.9%) and regional skin blood flow (+260.3%, P<0.01, ANOVA; each parameter). In contrast, PACAP did not cause any change in middle cerebral artery blood flow velocity or systemic hemodynamics. Our findings indicate that the vasculatures of the eye and the skin are particularly sensitive to PACAP and may implicate a potential role for this peptide in the regulation of blood flow in these vascular beds.


[Spinal and cerebral leptomeningeal seeding from a melanocytoma of the cerebello-pontine angle].
Meningeal melanocytoma refers to the uncommon clinical appearance of a generally benign tumour deriving from leptomeningeal melanocytes. Meningeal spread of this tumour is very rarely observed. We present the case of a 38-year-old man with meningeal melanocytoma of the cerebello-pontine angle, who showed a biphasic course of this disease, with a stable period followed by a steady progress within few months. After surgical resection of the melancytoma in the left skull base and of a first local recurrence five years later, a second local recurrence occurred 6 years after diagnosis, with intracerebral and spinal meningeal seeding. This tumor did not respond to a combined radiochemotherapy including oral temozolomide, and the patient died 5 months after starting treatment for this relapse. Secondary malignisation of the melancytoma is suggested.


Circulating levels of soluble Fas ligand reflect disease progression in multiple myeloma.
Multiple myeloma (MM) plasma cells are apoptosis resistant. The system of Fas with its ligand (Fas-L) participates actively in the extrinsic apoptotic system. In oncology, its role is controversial, since it has been reported both to suppress and promote tumor growth. The aim of this study was to measure serum levels of soluble Fas-L (sFas-L) in patients with active MM and to correlate them with markers of disease activity. We studied 57 patients with active MM, along with 22 healthy controls. We measured serum levels of sFas-L and interleukin-6 (IL-6) by enzyme-linked immunosorbent assays, as well of beta-2 microglobulin (B2M), C-reactive protein (CRP) and lactate dehydrogenase (LDH). We also measured the degree of bone marrow infiltration. All parameters were increased in patients, compared with controls (p < 0.001 for all cases) and also in parallel with disease stage (p < 0.001 for all cases). Positive correlations were noted between serum levels of sFas-L with IL-6, infiltration (p < 0.001 for both cases) and LDH (p < 0.04), but not with CRP and B2M. We suggest that the system of Fas/Fas-L participates actively in MM progression in a complex manner and that serum levels of sFas-L may reflect disease progression. Further studies are needed to determine its usefulness as a marker of disease activity.


Trospium 60 mg once daily (QD) for overactive bladder syndrome: results from a placebo-controlled interventional study.
A once-daily (QD) formulation of trospium chloride has been developed for the management of overactive bladder syndrome (OAB). This randomized controlled trial evaluated the efficacy and tolerability of this new extended-release formulation, trospium chloride 60 mg QD. Adults with OAB with urinary urgency, frequency, and urgency urinary incontinence (UUI) were eligible for inclusion. Subjects received trospium 60 mg QD or placebo for 12 weeks. Change in the mean number of toilet voids per day and UUI episodes per day were the primary outcome variables. Changes in urgency severity were also assessed and adverse events (AEs) were recorded. Overall, 564 subjects participated in the study (trospium QD 280; placebo 284). Trospium QD demonstrated significant improvement in both primary outcome variables. The mean number of toilet voids per day was reduced from approximately 13 at baseline to 10.3 for trospium QD versus 11.1 for placebo (P <0.001) at week 12, whereas the number of UUI episodes per day was reduced from approximately 4 at baseline to 1.7 at week 12 with trospium QD versus 2.4 for placebo (P <0.001). Trospium QD also reduced urgency severity (P <0.001) and increased voided volume (P <0.01) compared with placebo. Benefits over placebo were apparent within the first week of treatment. Trospium QD was well tolerated; the most frequent AEs being dry mouth (trospium QD 12.9%; placebo 4.6%) and constipation (7.5% versus 1.8%, respectively). Central nervous system side effects were rarely observed and were comparable between groups. Trospium QD represents a convenient, effective, and well-tolerated treatment option for OAB.


Nano-regenerative medicine towards clinical outcome of stem cell and tissue engineering in humans.
Nanotechnology is a fast growing area of research that aims to create nanomaterials or nanostructures development in stem cell and tissue-based therapies. Concepts and discoveries from the fields of bio nano research provide exciting opportunities of using stem cells for regeneration of tissues and organs. The application of nanotechnology to stem-cell biology would be able to address the challenges of disease therapeutics. This review covers the potential of nanotechnology approaches towards regenerative medicine. Furthermore, it focuses on current aspects of stem- and tissue-cell engineering. The magnetic nanoparticles-based applications in stem-cell research open new frontiers in cell and tissue engineering.


In situ generation of silver nanoparticles and nanocomposite films based on electrodeposition of carboxylated chitosan.
Herein, for the first time the electrodeposition of carboxylated chitosan is studied and utilized for the synthesis of silver nanoparticles (AgNPs) and generation of AgNPs/carboxylated chitosan nanocomposite films. Particularly, AgNPs are in situ synthesized on electrodes or substrates during the electrodeposition. Carboxylated chitosan not only acts as the green reducing agent and stabilizing agent for preparing AgNPs, but also serves as the main component in the electrodeposited nanocomposite film. The experimental results indicate that a smooth and homogeneous film is formed on the silver plate after electrodeposition, and the electrodeposited film can be detached from the silver plate as an independent film. The TEM observation and spectroscopic analysis results confirm the existence of AgNPs (the average size of 10 nm) in the nanocomposite film. The nanocomposite films with various shapes can be fabricated by the spatial selectivity of electrodeposition. In addition, the nanocomposite film containing AgNPs shows favorable antibacterial properties.


The structure of an oligo(dA).oligo(dT) tract and its biological implications.
Poly(dA).poly(dT) has unusual properties in that it cannot associate into nucleosomes and short, phased runs of it cause DNA bending. The crystal structure of a B-type DNA dodecamer containing a homopolymeric run of six A.T base pairs shows that this region possesses special structural features, including a system of bifurcated hydrogen bonds, which explains some of the properties of this simple homopolymer.


The liquid Kangfuxin (KFX) has efficient antifungal activity and can be used in the treatment of vulvovaginal candidiasis in mice.
Vulvovaginal candidiasis (VVC) is an infectious disease caused mainly by Candida albicans. Kangfuxin (KFX) is a traditional Chinese medicine preparation made from Periplaneta americana extracts, which promotes wound healing and enhances body immunity and also acts as an antifungal agent. Here, we evaluated the effect of KFX in the treatment of VVC in vitro and in vivo. The minimum inhibitory concentration (MIC50 ) of KFX against C. albicans ranged from 7·65 to 20·57%. In addition, KFX was more efficient than fluconazole (FLC) in inhibiting the drug-resistant C. albicans, and the effect was more intense after 8 h. The KFX treatment also exhibited good activity in vivo. It restored the body weight and reduced the vulvovaginal symptoms in mice induced with VVC. It downregulated the expression of the hyphae-related gene, HWP1, thus inhibiting the growth and development of C. albicans hyphae. It also increased the number of neutrophils and promoted the secretion of interleukin-17A (IL-17A); however, the levels of interleukin-8 (IL-8) and interleukin-1β (IL-1β) decreased in mice with VVC. We deduce that KFX effectively treats vaginal candidiasis in two ways: by inhibiting the growth and development of mycelia to reduce colonization of C. albicans and by promoting the secretion and release of IL-17A and neutrophils in high numbers to fight C. albicans infection. This study provides a theoretical basis for the use of KFX for the clinical treatment of VVC.


CT air trapping is independently associated with lung function reduction over time.
We aimed to study the association between lung function decline and quantitative computed tomography (CT) air trapping. Current and former heavy smokers in a lung cancer screening trial underwent volumetric low-dose CT in inspiration and expiration. Spirometry was obtained at baseline and after 3 years. The expiratory to inspiratory ratio of mean lung density (E/I-ratioMLD) was used to quantify air trapping. CT emphysema was defined as voxels in inspiratory CT below -950 Hounsfield Unit. Linear mixed modeling was used to determine the association between CT air trapping and lung function. We included 985 subjects with a mean age of 61.3 years. Independent of CT emphysema, CT air trapping was significantly associated with a reduction in forced expiratory volume in one second (FEV1) and the ratio of FEV1 over the forced vital capacity (FEV1/FVC); FEV1 declines with 33 mL per percent increase in CT air trapping, while FEV1/FVC declines 0.58% per percent increase (both p<0.001). CT air trapping further elicits accelerated loss of FEV1/FVC (additional 0.24% reduction per percent increase; p = 0.014). In a lung cancer screening cohort, quantitatively assessed air trapping on low-dose CT is independently associated with reduced lung function and accelerated decline of FEV1/FVC.


The effect of levamisole and albendazole on some enzymes of Ascaridia galli and Heterakis gallinae.
Ascaridia galli and Heterakis gallinae obtained from the common fowl Gallus gallus were exposed to 10(-2)-10(-5)M levamisole and albendazole; both compounds caused death of the parasites in vitro. The effect of the drugs was investigated on homogenates of the treated worms. Albendazole, at 10(-2)M, inhibited oxaloacetate reduction by 67 and 53% and malate oxidation by 21 and 17% in A. galli and H. gallinae, respectively, whereas 10(-4)M levamisole completely inhibited malate dehydrogenase activity in both directions in the two parasites. Lactate dehydrogenase was not affected significantly by either anthelmintic. Aldolase activity was diminished by 57 and 32% in A. galli and H. gallinae, respectively, with 10(-4)M levamisole. Levamisole at 10(-4)M also inhibited the activity of acid and alkaline phosphomonoesterase and cholinesterase. Albendazole had no significant effect on these enzymes in either parasite. Malate dehydrogenase and cholinesterase activity of the host tissue (intestine and caecum) was also reduced significantly with 10(-2) and 10(-3)M levamisole. These studies indicated a multiple mode of action of levamisole and albendazole.


Induction of mutations and sister-chromatid exchanges in Chinese hamster ovary cells by ethylating agents.
Chinese hamster ovary (CHO) cells were exposed to [3H]ethyl nitrosourea (ENU) or [3H]ethyl methanesulfonate (EMS) and the following DNA ethylation products were quantitated: 3- and 7-ethyladenine, O2-ethylcytosine, 3-, 7- and O6-ethylguanine, O2- and O4-ethyldeoxythymidine and the representative ethylated phosphodiester, deoxythymidylyl (3'-5')ethyl-deoxythymidine. When mutations at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus induced by these same treatments were compared with the observed ethylation products, mutations were found to correlate best with 3- and O6-ethylguanine. EMS induced approximately twice as many sister-chromatid exchanges (SCEs) as ENU at doses yielding equal mutation frequencies. When SCEs were indirectly compared with DNA ethylation products, 3-ethyladenine and ethylated phosphodiesters related best to SCE formation. Because mutation and SCE induction appear, at least in part, to be related to different DNA adducts, SCE induction by simple ethylating agents may not be a quantitative indicator of potentially mutagenic DNA damage.


Pinostrobin induces acute leukemia cell apoptosis via the regulation of miR-410-5p and SFRP5.
This study attempted to explore the mechanisms involved in pinostrobin (PN)-mediated acute leukemia cell apoptosis regulated by miR-410-5p. NB4 and MOLT-4 cells were cultured and treated with PN at the IC50 concentration. Apoptosis was examined by Annexin V-FITC/PI staining. RT-qPCR was used to measure the expression of caspase-3, BAK, BCL-W, and MCL-1. The target protein of PN was identified using LC-MS/MS followed by bioinformatic analysis. TargetScan, DIANA, and miRDB were used for the prediction of miRNAs involved in the PN-induced apoptosis mechanism. miRNA mimic transfection, RT-qPCR, and western blot analysis were performed to evaluate the regulatory effect of miRNA on its target and the involvement of miRNA in apoptosis induction by PN. In addition, the synergistic effect of PN and daunorubicin (DNR) were investigated by using the MTT assay. The results showed that PN reduced cell viability and induced apoptosis in both leukemia cell lines. From the LC-MS/MS and bioinformatics analysis, SFRP5 and miR-410-5p were selected as a potential PN target protein and miRNA, respectively. After miRNA mimic transfection, miR-410-5p, which is an onco-miRNA, was decreased and led to increased apoptosis in both cell lines, indicating that this miRNA is involved in PN-mediated apoptosis mechanisms. Moreover, PN demonstrated a synergistic effect with DNR, suggesting that PN may be used in combination with conventional chemotherapy drugs. PN regulates the expression of miR-410-5p and SFRP5 to promote apoptosis in acute leukemia cells. It could be developed as an alternative treatment for leukemia in the future.


Cell-to-cell bacterial interactions promoted by drier conditions on soil surfaces.
Bacterial cell-to-cell interactions are in the core of evolutionary and ecological processes in soil and other environments. Under most conditions, natural soils are unsaturated where the fragmented aqueous habitats and thin liquid films confine bacterial cells within small volumes and close proximity for prolonged periods. We report effects of a range of hydration conditions on bacterial cell-level interactions that are marked by plasmid transfer between donor and recipient cells within populations of the soil bacterium Pseudomonas putida Using hydration-controlled sand microcosms, we demonstrate that the frequency of cell-to-cell contacts under prescribed hydration increases with lowering water potential values (i.e., under drier conditions where the aqueous phase shrinks and fragments). These observations were supported using a mechanistic individual-based model for linking macroscopic soil water potential to microscopic distribution of liquid phase and explicit bacterial cell interactions in a simplified porous medium. Model results are in good agreement with observations and inspire confidence in the underlying mechanisms. The study highlights important physical factors that control short-range bacterial cell interactions in soil and on surfaces, specifically, the central role of the aqueous phase in mediating bacterial interactions and conditions that promote genetic information transfer in support of soil microbial diversity.


Defining the role of Emi1 in the DNA replication-segregation cycle.
Ordered progression through the cell cycle is essential to maintain genomic stability, and fundamental to this is ubiquitin-mediated proteolysis. In particular, the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase destabilises specific regulators at defined times in the cycle to ensure that each round of DNA replication is followed by cell division. Thus, the proper regulation of the APC/C is crucial in each cell cycle. There are several APC/C regulators that restrict its activity to specific cell cycle phases, and amongst these the early mitotic inhibitor 1 (Emi1) protein has recently come to prominence. Emi1 has been proposed to control APC/C in early mitosis; however, recent evidence questions this role. In this review we discuss new evidence that indicates that Emi1 is essential to restrict APC/C activity in interphase and, by doing so, ensure the proper coordination between DNA replication and mitosis.


Long-term Success of Cardioneuroablation in a Patient with Tachycardia-bradycardia Syndrome and Syncope.
A case of successful treatment for syncopal episodes caused by intermittent atrioventricular block in a patient with paroxysmal atrial fibrillation/atrial flutter using cardioneuroablation is presented.


Fluorescence-polarization changes in mononuclear blood leucocytes after PHA incubation: differences in cells from patients with and without neoplasia.
In 32 healthy blood donors, 20 patients with histologically verified cancer and 18 patients with non-neoplastic diseases, the fluorescence polarization changes of fluorescein samples incorporated in mononuclear leucotyes were measured after incubation with PHA. The leucocytes of healthy persons, and 16/18 persons with non-neoplastic diseases, responded with a decrease in the degree of fluorescence polarization by about 20% from that in non-PHA-stimulated cells. In 19/20 patients with a variety of malignant tumours, the leucotyes did not respond to PHA stimulation with such a decrease. The exceptions among the patients with neoplastic and non-neoplastic diseases are considered, and may not be "false-negative" or "false-positive" respectively, but indicative of a particular situation in that disease. The biophysical mechanisms underlying the observed changes remain to be investigated.


Arsenite binding to synthetic peptides: the effect of increasing length between two cysteines.
We utilized radioactive 73As-labeled arsenite and vacuum filtration methodology to determine the binding affinity of arsenite to eight synthetic peptides ranging from 13 to 24 amino acids long and containing one or two cysteines separated by 0-17 intervening amino acids. Six of the eight peptides were highly similar in amino acid sequence and were based on cysteine containing regions of the hormone-binding site of the human estrogen receptor-alpha (e.g., the sequence of peptide 28 is LEGAWCGKGVEGTEHLYSMKCKNV). The peptides with 0-14 intervening amino acids between two cysteines bound arsenite with Kd values of 2.7-20.1 uM and with Bmax values from 36 to 103 nmol/mg protein (from 0.083 to 0.19 nmol/nmol of protein). Thus, increasing the number of intervening amino acids from 0 to 14 made very little difference in the observed Kd values for arsenite, a surprising finding. Therefore, these peptides are flexible in solution and effectively contain a dithiol high affinity binding site for arsenite. Peptide 17 with two C separated by 19 amino acids bound arsenite with a Kd of 123 uM and a Bmax of 41.8 nmol/mg. The monothiol peptide 19 bound arsenite with a Kd of 124 uM and a Bmax of 26 nmol/mg protein. All experimental binding curves fit well to a one site binding model.


Determinants of long-term survival after ventricular aneurysmectomy.
To determine the effect of aneurysmectomy solely or combined with direct revascularization, 349 consecutive surgical patients treated between 1962 and 1972 were retrospectively reviewed. The minimum follow-up for survivors was 5 years (mean, 7 years). Single-vessel disease occurred in 171 (49%) and only ventricular aneurysmectomy was performed (Group 1). Multiple-vessel disease was found in 178 (51%), of whom 79 (44%) had resection of a ventricular aneurysm and revascularization of all major obstructed vessels (Group 2); 99 (56%) had aneurysm resection and incomplete revascularization (Group 3). Survival at 7 years was 69% for Group 1, 65% for Group 2, and 51% for Group 3. Actuarial survival at 7 years was 70% for patients operated on for angina; 55% for congestive heart failure; 57% for a combination of angina and heart failure; and 64% for ventricular tachycardia. Survival of patients with multiple-vessel disease who underwent aneurysmectomy and complete revascularization was similar to that of patients with single-vessel disease who underwent aneurysmectomy alone. Longevity is adversely influenced by incomplete revascularization (p less than 0.005) and preoperative congestive heart failure (p less than 0.005).


A Video-Based Module for Teaching Communication Skills to Otolaryngology Residents.
To determine whether instructional videos modeling examples of "good" and "bad" patient communication skills are useful as an educational tool for improving resident-patient communication. Retrospective study in which resident participants in the module gave survey responses indicating perceived utility of the exercise. Tertiary academic medical center. A total of 11 otolaryngology trainees from postgraduate year 1-5 who attended the course over 2 separate sessions and provided feedback on the benefits of the module. All 11 residents attended both sessions. Of 22 total survey responses, 21 found that the videos were "realistic and engaging" and were a true representation of commonly encountered clinical scenarios. Residents identified multiple themes and behaviors distinguishing "good" vs "bad" communication with patients and felt they could incorporate these into daily practice. A perceived weakness was the lack of opportunity for "role playing" with a video-based module as opposed to standardized patients. Instructional videos, when realistic, are useful for modeling effective patient communication skills for residents. By watching the videos, residents are able to identify specific techniques they can incorporate into their daily practice.


Dopamine and dopamine receptor D1 as a novel favourable biomarker for hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) remains one of the most common malignant tumours worldwide. Therefore, the identification and development of sensitivity- genes as novel diagnostic markers and effective therapeutic targets is urgently needed. Dopamine and dopamine receptor D1 (DRD1) are reported to be involved in the progression of various cancers. However, the crucial role of DRD1 in HCC malignant activities remains unclear. We enrolled 371 patients with liver hepatocellular carcinoma (LIHC) from The Cancer Genome Atlas (TCGA) to detect the expression and functions of DRD1. The Tumour Immune Estimation Resource (TIMER), UALCAN database, Kaplan-Meier plotter, cBioPortal database, and LinkedOmics database were utilized for the systematic investigation of DRD1 expression and related clinical features, coexpressed genes, functional pathways, mutations, and immune infiltrates in HCC. In this study, we determined that DRD1 expression was decreased in HCC tumour tissues versus normal tissues and that low DRD1 expression indicated a poor prognosis. The significance of DRD1 expression varied among different tumour samples. The somatic mutation frequency of DRD1 in the LIHC cohort was 0.3%. The biological functions of DRD1 were detected and validated, and DRD1 was shown to be involved in various functional activities, including metabolism, oxidation, mitochondrial matrix-related processes and other related signaling pathways. In addition, out study indicated that DRD1 had significant correlations with the infiltration of macrophages, B cells and CD+ T cells in HCC. These findings demonstrated the rationality of the potential application of DRD1 function as a novel biomarker for HCC diagnosis and a therapeutic target for HCC treatment.


Polymorphisms in the IL-6 and TNF-α gene are associated with an increased risk of abdominal aortic aneurysm.
An abdominal aortic aneurysm (AAA) is a complex disease of the aging population that is associated with inflammation and the cellular immune response. To investigate the influence of interleukin (IL)-6 and tumor necrosis factor (TNF)-α single nucleotide polymorphisms (SNPs) on the risk of AAA formation and progression, the frequency of AAA and its associated risk factors were determined. Four SNPs in the IL-6 (-174G/C, rs1800795; -572G/C, rs1800796) and TNF-α (-238G/A, rs361525; -308G/A, rs1800629) genes were studied by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in patients with AAA and healthy volunteers. The mRNA expression and plasma IL-6 and TNF-α levels were also determined. A mutation detected in at least one allele of the IL-6 -174G/C SNP was associated with a 2-fold increased risk of AAA occurrence (OR: 2.08; 95% CI: 1.15-3.76; p = 0.014, in the dominant model). An increased risk of AAA incidence among heterozygous carriers of the TNF-α - 308G/A genotype was observed (OR: 2.06; 95% CI: 1.17-3.62; p = 0.011, in the overdominant model). The wild-type genotypes of the IL-6 -174G/C and the TNF-α -308G/A SNPs coexisted more frequently in healthy subjects than in AAA patients and was associated with decreased risk of AAA (p < 0.001). Moreover, elevated levels of IL-6 and TNF-α were associated with an increased risk of hypertension (p < 0.001 and p = 0.022, respectively). The IL-6 -174G/C and the TNF-α -238G/A gene polymorphisms are associated with an increased risk of abdominal aortic aneurysm development.


Specific growth rate governs AOX1 gene expression, affecting the production kinetics of Pichia pastoris (Komagataella phaffii) PAOX1-driven recombinant producer strains with different target gene dosage.
The PAOX1-based expression system is the most widely used for producing recombinant proteins in the methylotrophic yeast Pichia pastoris (Komagataella phaffii). Despite relevant recent advances in regulation of the methanol utilization (MUT) pathway have been made, the role of specific growth rate (µ) in AOX1 regulation remains unknown, and therefore, its impact on protein production kinetics is still unclear. The influence of heterologous gene dosage, and both, operational mode and strategy, on culture physiological state was studied by cultivating the two PAOX1-driven Candida rugosa lipase 1 (Crl1) producer clones. Specifically, a clone integrating a single expression cassette of CRL1 was compared with one containing three cassettes over broad dilution rate and µ ranges in both chemostat and fed-batch cultivations. Chemostat cultivations allowed to establish the impact of µ on the MUT-related MIT1 pool which leads to a bell-shaped relationship between µ and PAOX1-driven gene expression, influencing directly Crl1 production kinetics. Also, chemostat and fed-batch cultivations exposed the favorable effects of increasing the CRL1 gene dosage (up to 2.4 fold in qp) on Crl1 production with no significant detrimental effects on physiological capabilities. PAOX1-driven gene expression and Crl1 production kinetics in P. pastoris were successfully correlated with µ. In fact, µ governs MUT-related MIT1 amount that triggers PAOX1-driven gene expression-heterologous genes included-, thus directly influencing the production kinetics of recombinant protein.


Gone fishing in a fluid trial.
To maximise the yield of existing data by assessing the effect on mortality of being born under the zodiac sign Pisces in a trial of intravenous (IV) fluids. A retrospective observational study, with no predefined hypothesis or statistical analysis plan, of 26 Scandinavian intensive care units between 2009 and 2011. Patients aged 18 years or older with severe sepsis and in need of fluid resuscitation, randomised in the Scandinavian Starch for Severe Sepsis/ Septic Shock (6S) trial. Ninety-day mortality. We included all 798 randomised patients in our study; 70 (9%) were born under the sign of Pisces. The primary outcome (death within 90 days after randomisation) occurred in 25 patients (35.7%) in the Pisces group, compared with 348 patients (48%) in the non-Pisces group (relative risk, 0.75; 95% CI, 0.54-1.03; one-sided P = 0.03). In a multicentre randomised clinical trial of IV fluids, being born under the sign of Pisces was associated with a decreased risk of death. Our study shows that with convenient use of statistics and an enticing explanatory hypothesis, it is possible to achieve significant findings in post-hoc analyses of data from large trials.


Associations Between Late-Onset Preeclampsia and the Use of Calcium-Based Antacids and Proton Pump Inhibitors During Pregnancy: A Prospective Cohort Study.
Preeclampsia is a leading cause of maternal morbidity and mortality. Calcium-based antacids and proton pump inhibitors (PPIs) are commonly used during pregnancy to treat symptoms of gastroesophageal reflux disease. Both have been hypothesized to reduce the risk of preeclampsia. We determined associations of calcium-based antacid and PPI use during pregnancy with late-onset preeclampsia (≥34 weeks of gestation), taking into account dosage and timing of use. We included 9058 pregnant women participating in the PRIDE Study (2012-2019) or The Dutch Pregnancy Drug Register (2014-2019), two prospective cohorts in The Netherlands. Data were collected through web-based questionnaires and obstetric records. We estimated risk ratios (RRs) for late-onset preeclampsia for any use and trajectories of calcium-based antacid and PPI use before gestational day 238, and hazard ratios (HRs) for time-varying exposures after gestational day 237. Late-onset preeclampsia was diagnosed in 2.6% of pregnancies. Any use of calcium-based antacids (RR 1.2 [95% CI 0.9-1.6]) or PPIs (RR 1.4 [95% CI 0.8-2.4]) before gestational day 238 was not associated with late-onset preeclampsia. Use of low-dose calcium-based antacids in gestational weeks 0-16 (<1 g/day; RR 1.8 [95% CI 1.1-2.9]) and any use of PPIs in gestational weeks 17-33 (RR 1.6 [95% CI 1.0-2.8]) seemed to increase risks of late-onset preeclampsia. We did not observe associations between late-onset preeclampsia and use of calcium-based antacids (HR 1.0 [95% CI 0.6-1.5]) and PPIs (HR 1.4 [95% CI 0.7-2.9]) after gestational day 237. In this prospective cohort study, use of calcium-based antacids and PPIs during pregnancy was not found to reduce the risk of late-onset preeclampsia.


Correction: Online Guide for Electronic Health Evaluation Approaches: Systematic Scoping Review and Concept Mapping Study.
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Model-based subcutaneous insulin for glycemic control of pre-term infants in the neonatal intensive care unit.
Hyperglycaemia is a common problem in neonatal intensive care units (NICUs). Achieving good control can result in better outcomes for patients. However, good control is difficult, where poor control and resulting hypoglycaemia reduces outcomes and confounds results. Clinically validated models can provide good control, and subcutaneous insulin delivery can provide more options for insulin therapy for clinicians. However, this combination has only been significantly utilised in adult outpatient diabetes, but could hold benefit for treating NICU infants. This research combines a well-validated NICU metabolic model with subcutaneous insulin kinetics models to assess the feasibility of a model-based approach. Clinical data from 12 very/extremely pre-mature infants was collected for an average study duration of 10.1 days. Blood glucose, interstitial and plasma insulin, as well as subcutaneous and local insulin were modelled, and patient-specific insulin sensitivity profiles were identified for each patient. Modelling error was low, where the cohort median [IQR] mean percentage error was 0.8 [0.3 3.4] %. For external validation, insulin sensitivity was compared to previous NICU cohorts using the same metabolic model, where overall levels of insulin sensitivity were similar. Overall, the combined system model accurately captured observed glucose and insulin dynamics, showing the potential for a model-based approach to glycaemic control using subcutaneous insulin in this cohort. The results justify further model validation and clinical trial research to explore a model-based protocol.


Osteoporosis genetics: year 2011 in review.
Increased rates of osteoporotic fractures represent a worldwide phenomenon, which result from a progressing aging in the population around the world and creating socioeconomic problems. This review will focus mostly on human genetic studies identifying genomic regions, genes and mutations associated with osteoporosis (bone mineral density (BMD) and bone loss) and related fractures, which were published during 2011. Although multiple genome-wide association studies (GWAS) were performed to date, the genetic cause of osteoporosis and fractures has not yet been found, and only a small fraction of high heritability of bone mass was successfully explained. GWAS is a successful tool to initially define and prioritize specific chromosomal regions showing associations with the desired traits or diseases. Following the initial discovery and replication, targeted sequencing is needed in order to detect those rare variants which GWAS does not reveal by design. Recent GWAS findings for BMD included WNT16 and MEF2C. The role of bone morphogenetic proteins in fracture healing has been explored by several groups, and new single-nucleotide polymorphisms present in genes such as NOGGIN and SMAD6 were found to be associated with a greater risk of fracture non-union. Finding new candidate genes, and mutations associated with BMD and fractures, also provided new biological connections. Thus, candidates for molecular link between bone metabolism and lactation (for example, RAP1A gene), as well as possible pleiotropic effects for bone and muscle (ACTN3 gene) were suggested. The focus of contemporary studies seems to move toward whole-genome sequencing, epigenetic and functional genomics strategies to find causal variants for osteoporosis.


A mechanism for Ikaros regulation of human globin gene switching.
The human beta globin locus consists of an upstream LCR and functional genes arranged sequentially in the order of their expression during development: 5'-HBE1, HBG2, HBG1, HBD, HBB-3'. Haemoglobin switching entails the successive recruitment of these genes into an active chromatin hub (ACH). Here we show that the transcription factor Ikaros plays a major role in the formation of the beta-globin ACH, and in haemoglobin switching. In Plastic mice, where the DNA-binding region of Ikaros is disrupted by a point mutation, there is concomitant marked down-regulation of HBB, and up-regulation of HBG expression. We show for the first time Ikaros and its family member Eos, bind to critical cis elements implicated in haemoglobin switching and deletional hereditary persistence of fetal haemoglobin (HPFH). Chromatin conformation capture (3C) data demonstrated that Ikaros facilitates long-distance DNA looping between the LCR and a region upstream of HBD. This study provides new insights into the mechanism of stage-specific assembly of the beta-globin ACH, and HPFH.


Content validity of the Scoliosis Research Society questionnaire (SRS-22r): A qualitative concept elicitation study.
Scoliosis Research Society-22 revised (SRS-22r) is the common questionnaire used to evaluate health related quality of life (HRQOL) for young people with adolescent idiopathic scoliosis (AIS). The aim of this study is to evaluate its content validity for this population. In-depth semi-structured interviews were conducted with a purposive sample of young people with AIS (Cobb angle ≥25˚, aged 10-18 years). Concept elicitation was used to evaluate the influence of AIS on participants' HRQOL. Participant information sheets and consent/assent forms were age relevant. Topic guide was informed by the SRS-22r and existing evidence. Interviews were audio and video recorded, transcribed verbatim, coded, and analysed using thematic analysis. Derived themes/codes were compared with SRS-22r contents (domains/items). Eleven participants (mean age 14.9 years [SD = 1.8]; 8 female) were recruited. The mean curve size was 47.5° [SD = 18°] and participants had been managed via different approaches. Four main themes emerged with associated subthemes: 1) Physical effects related to physical symptoms (back hurt, stiffness) and body asymmetry (uneven shoulders), 2) Activity-related effects showed impact on mobility (sitting for long periods), self-care (dressing), and school activities (focus during lessons), 3) Psychological effects revealed emotional (feel worried), mental (sleep quality), and body image effects (hide back from others), 4) Social effects (participation in school and leisure activities), and school, friends and mental health support. A weak association was found between items of the SRS-22r and the identified codes. The SRS-22r does not adequately capture important concepts that relate to HRQOL of adolescents with AIS. These findings support revision of the SRS-22r, or the development of a new patient reported outcome measure to evaluate HRQOL of adolescents with AIS.


Haematogenous dissemination of cells from human renal adenocarcinomas.
Estimates were made of the rates at which cancer cells were released directly into the renal vein in patients undergoing radical nephrectomy for primary renal cancer. Cancer cells were counted in blood samples taken from the renal vein using a density gradient centrifugation procedure, and identified using immunocytochemical techniques, on the basis of their cytoskeletal intermediate filament proteins. Cancer cells were released as single cells and multicell emboli in 8/10 patients, in numbers varying widely between 14-7509 emboli ml-1 of blood. Despite a calculated median input into the metastatic process of 3.7 x 10(7) cancer cells per day for at least 180 days, only 3/10 patients had extraperitoneal metastases prior to surgery and only 1 of the remaining disease-free patients subsequently developed distant metastases over a maximum 35 month period. These results are discussed in terms of primary tumour kinetics and metastatic inefficiency.


Presence of somatostatin, enkephalins, and substance P-like peptides in cultured neurons from embryonic chick cerebral hemispheres.
The presence of peptides in pure cultures of neurons from 8-day-old chick embryo cerebral hemispheres has been investigated by means of specific radioimmunoassays and chromatographic purification. Somatostatin, Met-enkephalin, Leu-enkephalin, and substance P immunoreactive substances have been detected in 8-day-old cultures grown in serum-free culture medium. The peptides were present in the cellular extracts, as well as in the culture medium extracts. beta-Endorphin, thyroliberin, luteinizing hormone-releasing hormone, and ACTH could not be detected. The largest amount was accounted by somatostatin (48 +/- 2 ng/mg protein). Some 60% of the somatostatin-immunoreactive material was found in the culture medium. Met-enkephalin, Leu-enkephalin, and substance P were present at lower concentrations: 1.61 +/- 0.27, 0.24 +/- 0.02, and 0.14 +/- 0.005 ng/mg protein, respectively. The identities of somatostatin- and enkephalin-immunoreactive materials were confirmed by high pressure liquid chromatography. The findings suggest that cultured neurons that express dopaminergic and GABAergic properties contain peptides similar, if not identical, to somatostatin, Met-enkephalin, Leu-enkephalin, and substance P.


Changes in functional connectivity dynamics associated with vigilance network in taxi drivers.
An increasing number of neuroimaging studies have suggested that the fluctuations of low-frequency resting-state functional connectivity (FC) are not noise but are instead linked to the shift between distinct cognitive states. However, there is very limited knowledge about whether and how the fluctuations of FC at rest are influenced by long-term training and experience. Here, we investigated how the dynamics of resting-state FC are linked to driving behavior by comparing 20 licensed taxi drivers with 20 healthy non-drivers using a sliding window approach. We found that the driving experience could be effectively decoded with 90% (p<0.001) accuracy by the amplitude of low-frequency fluctuations in some specific connections, based on a multivariate pattern analysis technique. Interestingly, the majority of these connections fell within a set of distributed regions named "the vigilance network". Moreover, the decreased amplitude of the FC fluctuations within the vigilance network in the drivers was negatively correlated with the number of years that they had driven a taxi. Furthermore, temporally quasi-stable functional connectivity segmentation revealed significant differences between the drivers and non-drivers in the dwell time of specific vigilance-related transient brain states, although the brain's repertoire of functional states was preserved. Overall, these results suggested a significant link between the changes in the time-dependent aspects of resting-state FC within the vigilance network and long-term driving experiences. The results not only improve our understanding of how the brain supports driving behavior but also shed new light on the relationship between the dynamics of functional brain networks and individual behaviors.


[Results of treatment of the cancer of the larynx at the ENT-University-Clinic, Halle/Saale, 1940 to 1969 (author's transl)].
The treatment-surgery and irradiation- of 722 patients with cancer of the larynx in the years 1940-1969 are being statistically evaluated. The classification was done accordingly to localisation, stage (TNM-system) and the kind of therapy. The evaluation of the results only considers the 5-years-healing. Surgical therapy and primary irradiation were confronted. The irradiation ranks equally to surgery only at stages I and II of the carcinoma of the vocal cords. Tumors at other localisation or at a different stage (III and IV) can only be successfully treated by surgery.


Outcomes of trans-tibial posterior cruciate ligament reconstruction using a fovea landmark technique in relation to tunnel position and serial tunnel configuration.
To evaluate (1) the outcome of PCL reconstruction with tibial suspensory fixation using a fovea landmark technique based on the tunnel position and serial change of the tunnel configuration after trans-tibial PCL reconstruction, and (2) whether suspensory fixation has any harmful effect on the outcome. A total of 48 knees that underwent PCL reconstruction were included. The tunnel position was analyzed using CT. To analyze the tunnel configuration, the tunnel diameter, area, and volume were measured. To evaluate the outcome, pre- and postoperative International Knee Documentation Committee (IKDC) and Lysholm scores were analyzed. To evaluate stability, a side-to-side difference was evaluated using Telos stress radiographs. The greatest configurational change occurred at the mid-portion of tibial tunnel. There was a correlation between stability and tibial tunnel mid-portion configurational change (p < 0.01). Important correlations were found between the tunnel position and serial tunnel configuration between high femoral tunnel and widest site of femoral tunnel and tibia aperture (p < 0.01 and 0.04, respectively). The diameter of widest site of tibia tunnel increased when the tibia tunnel center moved toward the posterior margin of the tibia (p = 0.02) and the percentage of femoral tunnel volume enlargement increased when the tibia tunnel center moved toward the medial edge of the PCL fovea (p = 0.02). A high femoral tunnel, medial tibial tunnel, and posterior tibial tunnel were related to the serial configurational change. A suspensory tibial fixation produced significant configurational change around the mid-portion of the tibial tunnel, and it induced a negative effect on stability. Level IV.


Effects of exogenous neuraminidase on unit activity in frog spinal cord and fish optic tectum.
The effect of exogenous neuraminidase on spontaneous and evoked synaptic activity was investigated following injection of the enzyme into frog spinal cord and into cord and into the carp optic tectum. 1. Injection of enzyme into spinal cord segments caused a significant increase of motoneuron activity in the corresponding spinal nerve, which lasted for 7--31 min. 2. The amplitude of postsynaptic evoked potentials in the optic tectum was increased after neuraminidase injection up to 200% of control level for 20--40 min, whereas the amplitude of summed action potentials of retino-tectal afferents remained unchanged. 3. Similar effects were observed in single cell responses of the optic tectum with some differences in the degree of increase in activity, as well as latency and final depression of the stimulus response. 4. The extent of neuraminic acid liberation following neuraminidase treatment was determined biochemically. In both tissues investigated the amount of free neuraminic acid was increased significantly (4--5.5 fold) after enzyme treatment. Whereas after enzyme injection into spinal cord and optic tectum the percentage release of total glycoprotein- and glycolipidbound neuraminic acid was 12% and 15%, respectively, liberation from enzyme incubated tissue homogenates was somewhat higher (20.5% and 24%).


Emergence of SHV-12 extended spectrum beta-lactamase among clinical isolates of Enterobacter cloacae in Tunisia.
A collection of seven multidrug-resistant clinical isolates of Enterobacter cloacae with reduced susceptibility to ceftazidime and cefepime recovered from 2009 to 2010 at the University Hospital of Mahdia, Tunisia, was analysed. PCR analysis and sequencing demonstrated that all study isolates harbored SHV-12 β-lactamase that was transferred by conjugation. Characterization of the regions surrounding the bla(SHV-12) showed that this gene was flanked by two IS26 elements. pulsed-field gel electrophoresis (PFGE) revealed differents profiles indicating that the study isolates were not clonally related. Diffusion of E. cloacae producing SHV-12 ESBL in our hospital is the consequence of disseminations of plasmids harboring the SHV-12 gene.


Association of race and socioeconomic status and outcomes of patients with rectal cancer.
Few studies have evaluated disparities of race and socioeconomic status (SES) with outcomes in patients with rectal cancer. We hypothesize that disparities exist in the treatment and outcomes among patients with rectal cancer. Medical records of all patients with rectal cancer treated from 2000 to 2009 at an NCI cancer center (Fox Chase Cancer Center) and an urban academic center (Temple University Hospital) were retrospectively reviewed from a prospectively maintained tumor registry database. SES was estimated using census data. Quartiles of income and education based on zip codes were calculated. Lowest vs other quartiles were compared. Clinicopathologic variables included: initial stage, chemotherapy refusal, sphincter preservation, and overall survival (OS). A total of 748 patients were included in the analysis (581 white, 135 black, 6 other, 26 unknown). No difference in race, SES, or insurance status was seen with regard to stage at presentation. Chemotherapy and radiation refusal was rare. After excluding stage IV patients; sphincter preservation was more common among those with higher income. Median OS for all stages was worse for nonwhite patients (31 vs 50 months, p < .001), and those with low income and education. OS disparities were most pronounced among nonwhite patients with advanced disease. Insurance was not associated with a survival difference. Age, stage, and race were independent predictors of survival. Disparity exists in outcomes of patients with rectal cancer. Nonwhite race is associated with worse OS, and lower SES is associated with lower OS and sphincter preservation among patients with rectal cancer.


Iron deficiency and early childhood caries: a systematic review and meta-analysis.
Previous surveys have found that children with iron deficiency (ID) were likely to suffer from early childhood caries (ECC). We aimed to assess the scientific evidence about whether ID is intrinsically related to ECC. The medical subject headings (MeSH) terms and free words were searched on PubMed, Web of Science, Cochrane, China National Knowledge Infrastructure, Wanfang, and the Database for Chinese Technical Periodicals from March 2020 to September 2020. Two researchers independently screened the articles. Data extraction and cross-checking were performed for the studies that met the inclusion criteria. Meta-analysis was performed using the Cochrane Collaboration's Review Manager 5.3 software. After excluding duplication and irrelevant literature, 12 case-control studies were included in the study. The meta-analysis demonstrated that children with ECC were more likely to have ID (odds ratio [OR] = 2.63, 95% confidence interval [CI]: [1.85, 3.73], P < 0.001). There was no statistically significant association found between the level of serum ferritin and ECC (weighted mean difference (WMD) = -5.80, 95% CI: [-11.97, 0.37], P = 0.07). Children with ECC were more likely to have iron-deficiency anemia (OR = 2.74, 95% CI: [2.41,3.11], P < 0.001). The hemoglobin (HGB) levels in the ECC group were significantly lower compared with that in the ECC-free group (WMD = -9.96, 95% CI: [-15.45, -4.46], P = 0.0004). The mean corpuscular volume (MCV) levels in the ECC group were significantly lower compared with that in the ECC-free group (WMD = -3.72, 95% CI: [-6.65, -0.79], P = 0.01). ID was more prevalent in children with ECC, and the markers of iron status in the ECC group, such as serum ferritin, HGB, and MCV, were relatively lower than the ECC-free group.


A histopathologic study of gastric and small intestinal graft-versus-host disease following allogeneic bone marrow transplantation.
Twenty-two stomach and 14 small intestinal biopsy specimens from 24 allogeneic bone marrow transplant recipients were reviewed to evaluate the histopathologic changes of graft-versus-host disease (GVHD) in these organs. Associations between these results and clinical symptoms and other biopsy results were sought. In both organs, single epithelial cell necrosis was found to correlate with GVHD. Gastric GVHD was diagnosed in eight patients and small intestinal GVHD in four. Gastric GVHD was characterized by nausea, vomiting, and upper abdominal pain without diarrhea (the latter being present in only two patients), while all four of the patients with small intestinal GVHD had upper gastrointestinal symptoms and diarrhea. These symptoms correlated with concurrent rectal biopsy findings; pathologic alterations were seen in only one of six specimens from patients with gastric GVHD but in three of four with small intestinal GVHD. These findings suggest that stomach biopsy may be necessary to diagnose GVHD in patients with upper gastrointestinal symptoms but no diarrhea and normal rectal biopsy specimens. Diagnostic problems may arise in the early posttransplantation period, when the effects of cytoreductive therapy may simulate GVHD, and in patients with gastrointestinal cytomegalovirus infection, which may also produce changes identical to those of GVHD.


Does distracting pain justify performing brain computed tomography in multiple traumas with mild head injury?
Traumatic brain injury (TBI) is a significant health concern classified as mild, moderate, and severe. Although the indications to perform brain computed tomography (CT) are clear in moderate and severe cases, there still exists controversy in mild TBI (mTBI). We designed the study to evaluate the significance of distracting pain in patients with mTBI. The study population included patients with mild traumatic brain injury (GCS ≥13). Moderate and high risk factors including age <18 months or ≥60 years, moderate to severe or progressive headache, ≥2 episodes of vomiting, loss of consciousness (LOC), post-traumatic amnesia, seizure or prior antiepileptic use, alcohol intoxication, previous neurosurgical procedures, uncontrolled hypertension, anticoagulant use, presence of focal neurologic deficits, deformities in craniofacial region, and penetrating injuries were excluded. The patients were then grouped based on presence (DP+) or absence (DP-) of another organ fracture with severe pain (based on VAS). The primary outcome was any abnormal findings on brain CT scans; 330 patients were enrolled (184 DP+ and 146 DP-). Overall, two DP+ and one DP- patients had mild cerebral edema in brain CT (p > 0.99). No patients had any neurologic symptoms or signs in follow-up. Our results show that in the absence of any other risk factors, distracting pain from other organs (limbs, pelvis, and non-cervical spine) cannot be regarded as a brain CT indication in patients with mild TBI, as it is never associated with significant intracranial lesions.


Preparing the Allergist/Immunologist for the Next Pandemic.
The COVID-19 pandemic had a profound impact on society in general and allergists' practices in particular. The adverse effects included a loss of practice productivity and income, staffing, and in-office procedures due to concerns about the spread of infection and the need for social/physical distancing as well as isolation. Allergy training programs and research activities also suffered. Federal financial assistance, rapid adoption of telehealth with Medicare waivers, and adaptation of practice sites, training programs, and research activities allowed for some return to normal, although still with significant restrictions in staffing and in-office procedures. There were positive aspects to the pandemic in the form of telehealth initiatives, pathways for rapid development and approval of tests and treatments, opportunities for new collaborations, and expertise in vaccines. Preparation for the next pandemic needs to be considered now to avoid the mistakes and missteps that occurred with the COVID-19 pandemic. On a national level, a strategy to overcome the societal divisions, misinformation/disinformation, and distrust of science needs to be developed based on better communication, as well as advocacy for continued improvement in our public health system. Practices and training programs as well as research centers need to institutionalize changes made during the pandemic so they can quickly be reinitiated when necessary.


A comprehensive policy for reducing sugar beverages for healthy life extension.
The excessive consumption of sugar-sweetened beverages is a public health concern worldwide. Several clinical trials examining the effects of consuming sucrose or high-fructose corn syrup demonstrated the link between this consumption and increased risk factors for cardiometabolic diseases. In this issue of Environmental Health and Preventive Medicine, Li et al. examined the sugar-sweetened beverage consumption among undergraduate students and evaluated the relationship between this consumption and the "late" chronotype, sleep duration, and weight increase. They concluded that the sugar-sweetened beverage intake might mediate the associations among sleep duration, late chronotype, and weight gain and that the intake of sugar-sweetened beverages in the evening may be a risk factor for the development of overweight/obesity. A systematic review and meta-analysis of prospective cohort studies and randomized controlled trials provided evidence that the consumption of sugar-sweetened beverages promotes weight gain in both children and adults. The World Health Organization guideline highly recommends reducing the intake of sugars to less than 10% of one's total energy intake. The Dietary Approaches to Stop Hypertension diet and the Mediterranean diet were shown to help individuals refrain from sweets and sugar-containing beverages. A global evaluation revealed how much disability during accumulated lifetime hours is due to sugar-sweetened beverages. Interventions are necessary, but many individuals find it quite difficult to reduce or eliminate their high intake of sugar-sweetened beverages. The taxation of sugar-sweetened beverages was demonstrated to have a significant positive influence on individuals' planned purchases and the probability of the purchase of healthy beverages. Western countries are working on the social regulation of sugar-sweetened beverages, but Japan has not implemented any similar regulations. The social regulation of sugar-sweetened beverages is necessary to stop the increase of diabetes morbidity and the increase in dementia that often accompanies this morbidity.


Effects of microplastic exposure on the early developmental period and circadian rhythm of zebrafish (Danio rerio): A comparative study of polylactic acid and polyglycolic acid.
Polyglycolic acid (PGA) is an emerging biodegradable plastic material. Together with polylactic acid (PLA), PGA is considered a suitable alternative to conventional plastics and has been widely used in biomedical and food packaging industries. However, degradable plastics continue to face the drawbacks of harsh degradation environment and long degradation time, and may harm the environment and the human body. Therefore, our study focused on assessing the effects of degradable microplastics PGA and PLA on the development and neurobehavior of zebrafish. The results showed that PGA and PLA had little effect on 3-10 hpf embryos. However, developmental stunting was observed in a100 mg/L PGA and PLA-exposed group at 24 hpf. In addition, PGA and PLA exposure decreased the survival and hatching rates, increased wakefulness, and reduced sleep in zebrafish. This indicates that PGA and PLA may affect the circadian behavior of zebrafish by affecting the brain-derived neurotrophic factor (BDNF). Therefore, our results suggest that PGA and PLA exposure induces developmental toxicity, reduces voluntary locomotion, induces of anxiety-like behaviors, and impairs sleep/wake behaviors in zebrafish larvae. This also suggests that the potentially toxic effects of degradable plastics cannot be ignored and that the biological effects of PGA require further research.


Miltefosine induces metacaspase and PARP genes expression in Leishmania infantum.
Apoptosis is the process of programmed cell death (PCD) that occurs in both animal and plant cells. Protozoan parasites possess metacaspase and these caspase-related proteases could be involved in the PCD pathways in these organisms. Therefore we analyzed the activities of metacaspase and PARP genes in Leishmania infantum (MCAN/IR/96/LON49) treated with miltefosine. Anti-leishmania activity of miltefosine was studied by treatment of cultured promastigotes with various concentration of miltefosine. MTT assay and Annexin-V FLUOS staining by using FACS flow cytometry methods were used. Cytotoxic potential of HePC on the amastigots of L.infantum was evaluated in J774 cell line. In addition, metacaspase and PARP genes expression of treated L. infantum were studied. Miltefosine led to dose-dependent death of L. infantum with features compatible with apoptosis. Over expression of metacaspase and PARP was seen 6 hr after treatment. Our study showed that miltefosine exerts cytotoxic effect on L. infantum via an apoptotic-related mechanism.


The deubiquitinase EIF3H promotes hepatocellular carcinoma progression by stabilizing OGT and inhibiting ferroptosis.
Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal human malignancies, and with quite limited treatment alternatives. The proteasome is responsible for most of the protein degradation in eukaryotic cells and required for the maintenance of intracellular homeostasis. However, its potential role in HCC is largely unknown. In the current study, we identified eukaryotic translation initiation factor 3 subunit H (EIF3H), belonging to the JAB1/MPN/MOV34 (JAMM) superfamily, as a bona fide deubiquitylase of O-GlcNAc transferase (OGT) in HCC. We explored that EIF3H was positively associated with OGT in HCC and was related to the unfavorable prognosis. EIF3H could interact with, deubiquitylate, and stabilize OGT in a deubiquitylase-dependent manner. Specifically, EIF3H was associated with the GT domain of ERα via its JAB/MP domain, thus inhibiting the K48-linked ubiquitin chain on OGT. Besides, we demonstrated that the knockdown of EIF3H significantly reduced OGT protein expression, cell proliferation and invasion, and caused G1/S arrest of HCC. We also found that the deletion of EIF3H prompted ferroptosis in HCC cells. Finally, the effects of EIF3H depletion could be reversed by further OGT overexpression, implying that the OGT status is indispensable for EIF3H function in HCC carcinogenesis. In summary, our study described the oncogenic function of EIF3H and revealed an interesting post-translational mechanism between EIF3H, OGT, and ferroptosis in HCC. Targeting the EIF3H may be a promising approach in HCC. Video Abstract.


A subset of Schwann cells in peripheral nerves contain a 50-kDa protein antigenically related to astrocyte intermediate filaments.
Antisera raised to the astrocyte intermediate filament structural protein stained elements in the peripheral nerves of several species. These elements were not associated with myelinated nerve fibers, were more common in splenic and vagus nerves than in the sciatic nerve, and persisted after nerve transection. In teased nerve preparations antigen-positive cells appeared to be the Schwann cells that surround small diameter, unmyelinated axons. Absorption of the antiserum with purified rat spinal cord 50-kDa protein or with bovine splenic nerve cytoskeletal extract blocked the reaction with CNS astrocyte processes or with PNS nerve fibers. Immunoblots of cytoskeletal preparations of bovine splenic nerve or rat sciatic nerve showed that the antigen from peripheral nerves comigrated at 50 kDa with antigen from bovine or rat spinal cord or cultured rat astrocytes. The CNS and PNS 50-kDa proteins from bovine tissues were subjected to limited digestion with Staphylococcus aureus protease V8. After separation on SDS-gels, antigenic peptides were detected by immunoblotting. The pattern of antigenic peptides for the CNS and PNS proteins were identical. We conclude that Schwann cells associated with nonmyelinated axons contain a cytoskeletal protein that is the same size and has the same peptide map as the major structural protein of astrocyte intermediate filaments.


Cortical transit time as a predictive marker of the need for surgery in children with pelvi-ureteric junction stenosis: preliminary study.
Postnatal management of prenatally detected hydronephrosis remains controversial. It has been suggested that cortical transit time (CTT) could successfully predict deterioration in children with pelvi-ureteric junction (PUJ) obstruction. We decided to conduct a retrospective study in our hydronephrosis population to evaluate whether initial CTT was significantly correlated with the need for surgery. We reviewed the charts of all our patients managed for significant PUJ obstruction (>12 mm) between 2007 and 2010 and determined CTT retrospectively, on the first diuretic scan of each of these patients. We then determined the relationship between initial CTT and the need for surgery. We identified 37 patients with hydronephrosis (pelvic size >12 mm) of which 26 were diagnosed prenatally. Out of 22 patients with an initial abnormal CTT, 20 underwent surgery. Out of 15 children with a normal initial CTT, 4 underwent surgery (OR 27.5 (IC95%: 4.3-174.9)). Initial CTT could be a reliable prognostic factor for future evolution of renal function in children with hydronephrosis. CTT is easy to determine on diuretic renal scan. A prospective trial is being devised to confirm what role it could have in the management of children with hydronephrosis.


Ventriculoperitoneal shunt procedure complicated by ureter obstruction. Case report.
The authors present the case history of a patient in whom the peritoneal catheter of a ventriculoperitoneal shunt system caused ureter obstruction. This is a rare complication of such a shunt procedure, and the patient's symptoms were relieved by shortening the peritoneal catheter.


Novel inclusion bodies in Betz cells of cortical area 4 of aged rhesus monkeys.
Seven adult rhesus monkeys ranging in age from 5 to 35 years were studied in an ultrastructural investigation of cortical area 4. Some Betz cells of layer 5 contained a perikaryal inclusion body (IB) of a unique and characteristic ultrastructural configuration that has not previously been described. The IBs consist of a regular array of three sets of equidistant parallel sheets and are not membrane bound. The distance between the sheets measures approximately 80 nm. The three sets of sheets intersect at an invariable angle of 60 degrees, forming a regular geometric structure. Each sheet comprises a single layer of parallel and densely packed straight filaments, which are approximately 10 nm thick. Thus the IBs present highly ordered crystalline arrays of filaments. The occurrence and number of IBs may be age related, since they appeared only in monkeys in mid to late adulthood and were most numerous in the oldest monkey.


Case identification of work-related traumatic brain injury using the occupational injury and illness classification system.
Traumatic brain injury (TBI) is one of the most common, costly, and disabling occupational injuries. Objectives included determining whether work-related TBI could be reliably identified using the Occupational Injury and Illness Classification System (OIICS) and describing challenges in developing an OIICS-based TBI case definition. Washington State trauma registry reports and workers' compensation claims were linked (1998 to 2008). Trauma registry diagnoses were used as the gold standard for six OIICS-based TBI case definitions. The OIICS-based case definitions were highly specific but had low sensitivity, capturing less than a third of fatal and nonfatal TBI. The use of OIICS versus International Classification of Diseases-Ninth Revision-Clinical Modification codes underestimated TBI and changed the attributable cause distribution, with potential implications for prevention efforts. Surveillance methods that can more fully and accurately capture the impact of work-related TBI across the United States are needed.


Contamination source identification in water distribution networks using convolutional neural network.
Contamination source identification (CSI) is significant for water quality security and social stability when a contamination intrusion event occurs in water distribution systems (WDSs). However, in research, this is an extremely challenging task for many reasons, such as limited number of water quality sensors and their limitations in detecting contaminants. Hence, some researchers have introduced consumers' complaint information as an alternative of sensors for CSI. But the problem with this approach is that the uncertainty of complaint delay time has a great impact on the identification accuracy. To address this issue, this study constructed complaint matrices to present the spatiotemporal characteristics of consumer complaints in an intrusion event and proposed a new methodology employing convolution neural network (CNN)-a deep learning algorithm-for the purpose of pattern recognition. CNN aimed to explore the inherent characteristics of complaint patterns corresponding to different contaminant intrusion nodes and to improve the performance of identifying the contamination source based on consumer complaint information. Two case studies illustrated methodology effectiveness in WDSs of various scales, even with the high uncertainties of complaint delay time. The comparison between CNN and a back-propagation artificial neural network algorithm demonstrates that the former framework possesses stronger robustness and higher accuracy for CSI.


Targeted Therapies for Epstein-Barr Virus-Associated Lymphomas.
The Epstein-Barr virus (EBV) is the first human tumor virus identified that can transform quiescent B lymphocytes into lymphoblastoid cell lines (LCLs) in vitro. EBV can establish asymptomatic life-long persistence and is associated with multiple human malignancies, including non-Hodgkin lymphoma and Hodgkin lymphoma, as well as infectious mononucleosis. Although EBV-associated lymphomagenesis has been investigated for over 50 years, viral-mediated transformation is not completely understood, and the development of EBV-specific therapeutic strategies to treat the associated cancers is still a major challenge. However, the rapid development of several novel therapies offers exciting possibilities to target EBV-induced lymphomas. This review highlights targeted therapies with potential for treating EBV-associated lymphomas, including small molecule inhibitors, immunotherapy, cell therapy, preventative and therapeutic vaccines, and other potent approaches, which are novel strategies for controlling, preventing, and treating these viral-induced malignances.


Role of fiberscopic transbronchial needle aspiration in the staging of N2 disease due to non-small cell lung cancer.
Transbronchoscopic needle aspiration (TBNA) can offer a unique opportunity to identify surgically unresectable lung cancer and to avoid surgical mediastinal exploration in many patients with mediastinal lymph node extension of the tumor. The aim of this study was to assess the yield of TBNA performed with either histology or cytology needles in mediastinal staging of N2 disease due to non-small cell lung cancer (NSCLC). Retrospective chart review was carried out on 194 TBNA procedures performed between January 1997 and September 2000 at a single institution. Inclusion criteria were pathologic evidence of NSCLC; contrast enhancement computed tomography scan of the chest suggesting N2 disease; and negative bronchoscopic examination for possible neoplastic lesions at the site of Overall sensitivity and diagnostic accuracy were 71% and 73%, respectively, with no significant differences between 19-gauge and 22-gauge cytology needles. Procedures performed for right paratracheal and subcarinal lymph node stations had a significantly higher yield than those for the left paratracheal station. TBNA mediastinal staging, performed during the initial diagnostic evaluation of NSCLC, can spare costs and risks of more invasive procedures in patients with inoperable tumors, in patients who are not candidates for operation because of coexistent significant comorbidities, and in patients with N2 disease.


Curcuma longa rhizome extract and Curcumin reduce the adhesion of Acanthamoeba triangularis trophozoites and cysts in polystyrene plastic surface and contact lens.
Curcuma longa and Curcumin have been documented to have a wide spectrum of pharmacological effects, including anti-Acanthamoeba activity. Hence, this study sought to explore the anti-adhesion activity of C. longa extract and Curcumin against Acanthamoeba triangularis trophozoites and cysts in plastic and contact lenses. Our results showed that C. longa extract and Curcumin significantly inhibited the adhesion of A. triangularis trophozoites and cysts to the plastic surface, as investigated by the crystal violet assay (P < 0.05). Also, an 80-90% decrease in adhesion of trophozoites and cysts to the plastic surface was detected following the treatment with C. longa extract and Curcumin at 1/2 × MIC, compared to the control. In the contact lens model, approximately 1 log cells/mL of the trophozoites and cysts was reduced when the cells were treated with Curcumin, when compared to the control. Pre-treatment of the plastic surface with Curcumin at 1/2-MIC reduced 60% and 90% of the adhesion of trophozoites and cysts, respectively. The reduction in 1 Log cells/mL of the adhesion of A. triangularis trophozoites was observed when lenses were pre-treated with both the extract and Curcumin. Base on the results obtained from this study, A. triangularis trophozoites treated with C. longa extract and Curcumin have lost strong acanthopodia, thorn-like projection pseudopodia observed by scanning electron microscope. This study also revealed the therapeutic potentials of C. longa extract and Curcumin, as such, have promising anti-adhesive potential that can be used in the management/prevention of A. triangularis adhesion to contact lenses.


Correlations between angiogenic factors and capillaroscopic patterns in systemic sclerosis.
We sought to assess whether nailfold videocapillaroscopy (NVC) patterns are associated with levels of angiogenic factors in systemic sclerosis (SSc). Circulating endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) were measured in the peripheral blood of 60 consecutive SSc patients. Serum levels of eight endothelial markers were measured first in these 60 patients, and then in an independent replication cohort of 43 SSc patients in case of association with NVC patterns. NVC patterns were determined by four independent investigators blinded to vascular markers. Patients with the late-NVC pattern exhibited lower EPC levels (P < 0.0001) and higher VEGF levels (P = 0.03). Higher VEGF levels were confirmed to be associated with the late-NVC pattern in the replication cohort (P = 0.01). By multivariate analysis focused on biomarkers, lower EPC (P = 0.03) and higher VEGF levels (P = 0.001) were independently associated with the late-NVC pattern. In an alternate multivariate model including these two factors and SSc-related disease characteristics, lower EPC counts (P = 0.005), higher VEGF levels (P = 0.01), a history of digital ulcers (P = 0.04), and a modified Rodnan skin score > 14 (P < 0.0001) were independently associated with the late-NVC pattern. Our data revealed decreased EPC counts and increased VEGF levels in patients with the late-NVC pattern. Further studies are now needed to determine the role of VEGF and EPCs in endothelial injury and repair in SSc.


Prednisolone pharmacokinetics in cushingoid and non-cushingoid kidney transplant patients.
Prednisolone pharmacokinetics and protein binding have been compared in 16 cushingoid and 46 non-cushingoid long-term kidney transplant recipients. After oral administration of 10 mg prednisolone, the cushingoid patients had a significantly higher peak prednisolone serum concentration (P less than 0.03), a longer elimination half-time (P less than 0.03), and a larger area under the time-concentration curve of total (P less than 0.01) and free (P less than 0.03) prednisolone. The apparent total body clearance of total and free prednisolone was significantly lower in the cushingoid than in the non-cushingoid patients (P less than 0.02 and less than 0.05, respectively). There was no significant difference in time of peak concentration, apparent volume of distribution or serum protein binding of prednisolone. It is suggested that the development and persistency of some cushingoid features may be related to a decreased total body clearance of prednisolone, which, in turn, may be influenced by impaired renal function.


Risk-Based Monitoring: A Closer Statistical Look at Source Document Verification, Queries, Study Size Effects, and Data Quality.
Data quality within the clinical research enterprise can be defined as the absence of errors that matter and whether the data are fit for purpose. This concept, proposed by the Clinical Trials Transformation Initiative, resulted from a culmination of collaboration with industry, academia, patient advocates, and regulators, and it emphasizes the presence of a hierarchy of error types, resulting in a more efficient and modern data-cleaning paradigm. While source document verification (SDV) is commonly used as a quality control method in clinical research, it is disproportionately expensive and often leads to questionable benefits. Although the current literature suggests that there is a need to reduce the burden of SDV, there is no consensus on how to replace this "tried and true" practice. This article proposes a practical risk-based monitoring approach based on published statistical evidence addressing the impact of database changes subsequent to SDV. The analysis clearly demonstrates minimal effects of errors and error corrections on study results and study conclusions, with diminishing effect as the study size increases, and it suggests that, on average, <8% SDV is adequate to ensure data quality, with perhaps higher SDV rates for smaller studies and virtually 0% SDV for large studies. It is recommended that SDV, rather than just focusing on key primary efficacy and safety outcomes, focus on data clarification queries as highly discrepant (and the riskiest) data.


Hemicraniectomy for middle cerebral artery infarction.
The space-occupying so-called "malignant" middle cerebral artery infarction is-besides acute basilar artery occlusion-the most devastating form of ischemic stroke. Until recently, there was no proven treatment. In 2007, results from randomized controlled trials provided evidence for the benefit of early hemicraniectomy with respect to mortality after 3 months. This review focuses on current treatment options for malignant ischemic brain infarction, especially hemicraniectomy. Moreover, major unsolved problems and open questions regarding the disease are discussed, and perspective is given on future clinical studies.


Purification and chemical characterization of papain-solubilized histocompatibility-2 antigens from mouse liver.
A large scale purification of histocompatibility-2 (H-2) antigens from mouse liver is described. The antigens were solubilized by a limited papain digestion of a crude preparation of liver membranes (strain A/J) and purified by ion exchange chromatography, gel filtration, affinity chromatography, and isoelectric focusing. The overall degree of purification of H-2Kk was 1,300-fold and that of H-2Dd was 1,500-fold; approximately 8 mg of purified H-2a antigens were obtained from 1 kg of liver. The purification was followed by a sensitive radioimmunoassay in which H-2a-containing fractions were used to inhibit the binding of 125I-labeled H-2a to appropriate antisera. H-2Dd and H-2Kk co-purified through all the steps but the concentration of H-2Kk was 2- to 3-fold higher than that of H-2Dd in the liver homogenate as well as in the purified H-2 preparation. beta 2-microglobulin was initially present in a 3- to 10-fold excess over H-2 in the liver homogenate, but the purified H-2 preparation contained approximately 2 mol of alloantigenic heavy chain/mol of beta 2-microglobulin. Isoelectric focusing and disc-gel electrophoresis showed a charge heterogeneity of H-2, with a mean isoelectric point of pH 4.9. Electrophoresis on sodium dodecyl sulfate gels showed one band. Denaturing conditions were required to remove beta 2-microglobulin and small amounts of impurities from H-2. The amino acid sequence of the first 27 residues of the isolated heavy chains was determined.