Population genetic studies of the Aka pygmies (Central Africa): a survey of red cell and serum enzymes.
Blood samples collected in a single Pygmy tribe, the Aka, living in Bokoka district (Central African Empire) were investigated with respect to the phenotype and gene frequencies of the following 12 enzyme systems: acid phosphatase, adenosine deaminase, adenylate kinase, carbonic anhydrase, esterase D, glucose-6-phosphate dehydrogenase, malate dehydrogenase, phosphoglucomutase 1, phosphoglucomutase 2, phosphogluconate dehydrogenase, superoxide dismutase and serum cholinesterase variants (locus E1 and E2). The data obtained in the study of genetic polymorphisms of this isolated and inbred population show a specific pattern with the following characteristics: the very low frequency of PGDB and pa alleles; the existence of two rare PGM variants at the PGM2 locus, typical PGM26Pyg (4.2%) and PGM29 (0.2%); the high frequency of the pr allele (10.8%) and CAII2 (8.22%) and ESD2 genes (18.4%). Furthermore, at the G6PD locus four distinct alleles have been found: the negroid GdA- (4%) and GdA+ (16%), the common GdB+ (79.2%)--, and the rare Gd+Ibadan Austin (0.7%). Cholinesterase typings disclosed the presence of the uncommon E1f and E1s genes distributed within a single breeding unit. The results are compared with other data previously reported on South African Khoisan and some Negroid populations; the particular genetic background of Pygmies is discussed.


Successful treatment of mu-heavy chain disease with fludarabine monophosphate: a case report.
Heavy chain diseases (HCD) are monoclonal lymphoproliferative disorders of B-cells characterized by the synthesis of truncated heavy chains without associated light chains. In patients with mu-HCD, which is a very rare form of HCD, neoplastic cells produce immunoglobulin M heavy chain. The prognosis for patients with mu-HCD is poor, and there is no specific treatment for mu-HCD. In this report, we present a patient with mu-HCD accompanied by splenomegaly and thrombocytopenia. We treated this patient with the fludarabine monophosphate therapy we use for patients with B-cell chronic lymphocytic leukemia. After 5 courses of fludarabine monophosphate treatment, the splenomegaly and thrombocytopenia improved. Fludarabine monophosphate therapy may be a new strategy to improve the prognosis of patients with mu-HCD.


Generation of open biomedical datasets through ontology-driven transformation and integration processes.
Biomedical research usually requires combining large volumes of data from multiple heterogeneous sources, which makes difficult the integrated exploitation of such data. The Semantic Web paradigm offers a natural technological space for data integration and exploitation by generating content readable by machines. Linked Open Data is a Semantic Web initiative that promotes the publication and sharing of data in machine readable semantic formats. We present an approach for the transformation and integration of heterogeneous biomedical data with the objective of generating open biomedical datasets in Semantic Web formats. The transformation of the data is based on the mappings between the entities of the data schema and the ontological infrastructure that provides the meaning to the content. Our approach permits different types of mappings and includes the possibility of defining complex transformation patterns. Once the mappings are defined, they can be automatically applied to datasets to generate logically consistent content and the mappings can be reused in further transformation processes. The results of our research are (1) a common transformation and integration process for heterogeneous biomedical data; (2) the application of Linked Open Data principles to generate interoperable, open, biomedical datasets; (3) a software tool, called SWIT, that implements the approach. In this paper we also describe how we have applied SWIT in different biomedical scenarios and some lessons learned. We have presented an approach that is able to generate open biomedical repositories in Semantic Web formats. SWIT is able to apply the Linked Open Data principles in the generation of the datasets, so allowing for linking their content to external repositories and creating linked open datasets. SWIT datasets may contain data from multiple sources and schemas, thus becoming integrated datasets.


Intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer: effect of bacillus Calmette-Guerin viability on treatment results.
We treated 40 patients with superficial bladder cancer via intravesical bacillus Calmette-Guerin for 1) prophylaxis against tumor recurrence, 2) residual carcinoma or 3) flat carcinoma in situ. A single course of intravesical bacillus Calmette-Guerin therapy was successful in 6 of 11 patients (55 per cent) treated for residual carcinoma and 6 of 12 (50 per cent) treated for carcinoma in situ. Of 17 patients receiving a single course of bacillus Calmette-Guerin for prophylaxis 11 remained free of tumor during short-term followup. A second course of therapy was administered to failures in each treatment category, which resulted in favorable responses in 5 of 6 patients treated for prophylaxis, 2 of 5 treated for residual tumor and 3 of 6 treated for carcinoma in situ. Over-all complete responses were achieved in 16 of 17 patients (94 per cent) treated for prophylaxis, 8 of 11 (73 per cent) for residual carcinoma and 8 of 12 (66 per cent) for carcinoma in situ, with a mean followup from the final treatment of 9.3, 12.3 and 7.9 months, respectively. Favorable results occurred more frequently among patients who exhibited a granulomatous inflammatory response in the bladder and delayed hypersensitivity skin test response to purified protein derivative. Marked variability in viability of bacillus Calmette-Guerin organisms was observed among different lots of bacillus Calmette-Guerin, and a direct relationship was observed between bacillus Calmette-Guerin vaccine viability and therapeutic efficacy. Most patients who failed initial therapy with a low viability lot of bacillus Calmette-Guerin responded favorably to re-treatment with a higher viability lot. The results suggest that the level of viability of each lot of bacillus Calmette-Guerin vaccine should be verified before clinical use.


Failure is an option: learning from unsuccessful proof-of-concept trials.
Recent statistics indicate that the attrition rates during drug development remain high. Lack of clinical efficacy has meanwhile become the most frequent cause for discontinuation of a drug development program. Consequently, attrition rates are highest in clinical Phase II, which usually includes the first evidence for pharmacodynamic action of the compound or, proof of concept. Interestingly, attrition is approximately 60-70% across a variety of therapeutic areas, including the central nervous system (where predictivity of animal models is usually low) and cardiovascular medicine (where animal models are considered to be more predictive). Obviously, the translation of animal data into clinical benefit remains suboptimal.


Hyaluronic acid-coated chitosan nanoparticles as targeted-carrier of tamoxifen against MCF7 and TMX-resistant MCF7 cells.
Tamoxifen (TMX) is used to treat hormone-receptor-positive breast cancers at early stages. This research aimed to assess the potential of NPs in targeted delivery of TMX against MCF7 and TMX-resistant MCF7 breast cancer cell lines. For this purpose, a targeted delivery system including chitosan NPs coated with hyaluronic acid (HA-CS NPs) was created and examined in vitro. Chitosan NPs were first fabricated and loaded with TMX using the ionic-gelation method to prepare a drug-delivery system. Then, TMX-loaded CS NPs were coated by crosslinking the amino groups of chitosan to the carboxylic group of hyaluronic acid. The developed TMX delivery system was then optimized and characterized for particle fabrication, drug release, and targeting against cancer cells. The HA-CS particle size was 210 nm and its zeta potential was +25 mv. The encapsulation efficiency of TMX in NPs was 55%. TMX released from the NPs in acidic pH (5-6) was higher than the physiological pH (7.4). The cytotoxic effect of TMX-loaded HA-CS NPs on MCF7 and TMX-resistant MCF7 cells was significantly higher than TMX-loaded CS NPs and free drug. The findings confirmed the significant suppressive impact of TMX-loaded HA-CS NPs on MCF7 and TMX-resistant MCF7 cancer cells compared to the TMX-loaded CS NPs and free TMX. Graphical abstract.


Bioinformatic analysis identifies key transcriptome signatures in temporal lobe epilepsy.
To identify transcriptome signatures underlying epileptogenesis in temporal lobe epilepsy (TLE). Robust rank aggregation analysis was used to integrate multiple microarrays in rodent models of TLE and determine differentially expressed genes (DEGs) in acute, latent, and chronic stages. Functional annotation and protein-protein interaction analysis were performed to explore the potential functions of the DEGs and identify hub genes with the highest intramodular connectivity. The association between hub genes and hippocampal sclerosis/seizure frequency was analyzed using publicly available RNA-sequencing datasets from TLE patients. We subsequently established a pilocarpine-induced status epilepticus (SE) model in rats and validated mRNA expression of hub genes by quantitative reverse transcription PCR (qRT-PCR). The DEGs in the acute, latent, and chronic phases of TLE in animal models were prominently enriched in inflammatory response. Hub genes identified in the acute phase mainly participated in biological processes including inflammation, blood-brain barrier damage, and cell adhesion. The hub genes in the latent phase were related to microglia/macrophage activation (Emr1 and Aif1) and phagocytosis (Cd68, Tyrobp, and Lyz). In the chronic phase, the hub genes were associated with activation of complements and microglia/macrophages. We further found that some hub genes identified in human TLE, such as Tlr2, Lgals3, and Stat3, were positively correlated with seizure frequency. Other hub genes, including Lgals3 and Serpine1, were associated with hippocampus sclerosis. qRT-PCR analysis confirmed that the mRNA levels of hub genes in rat hippocampus were significantly up-regulated after SE induction. Our integrated analysis identified hub genes in different stages of epilepsy. The functional annotations suggest that the activation and phagocytic activities of microglia/macrophages may play critical roles in epileptogenesis of TLE.


Lymph node status predicts the benefit of adjuvant chemoradiotherapy for patients with resected pancreatic cancer.
The role of adjuvant chemoradiotherapy in pancreatic cancer remains limited. The primary aim of this study was to determine the prediction of lymph node (LN) status to the benefit of adjuvant chemoradiotherapy for patients with resected pancreatic adenocarcinoma. Between December 2010 and December 2012, a total of 152 patients undergoing curative R0 resection for pancreatic adenocarcinoma from multi-institutions were retrospectively analyzed. Overall median survival was 16.3 months. Sixty-four patients (42.1%) received adjuvant chemoradiotherapy, whereas 88 (57.9%) did not receive adjuvant therapy after surgery. Patients who received chemoradiotherapy could achieve an improved median OS compared with surgery alone (20.3 versus 13.9 months, p=0.027). Stratified by different lymph node status, multivariate analysis demonstrated the benefit of adjuvant chemoradiotherapy was only seen among patients with lymphatic positive disease (HR = 0.54, 95% CI, 0.33-0.88; p=0.014), not lymphatic negative disease (HR = 0.80, 95% CI, 0.44-1.46; p=0. 468). This study suggests adjuvant chemoradiotherapy is associated with a significant improvement of survival only in patients with LN-positive disease, while the effects of chemoradiotherapy on patients with LN-negative disease may be limited. This study may add incremental knowledge of the role of lymph node status in offering treatment with adjuvant chemoradiotherapy.


Modifications in the laminar organization of peptide-like immunoreactivity in the anuran optic tectum following retinal deafferentation.
Substance P (SP)-, leucine-enkephalin (LENK)-, cholecystokinin octapeptide (CCK8)-, bombesin (BOM)-, and avian pancreatic polypeptide (APP)-like immunoreactivities were analyzed in the optic tectum of Rana pipiens 5-99 days after unilateral eye enucleation, or optic nerve ligation, by means of the peroxidase-antiperoxidase and indirect fluorescence single and double labeling methods. The normal pattern (Kuljis and Karten, '81, '82c) of peptide-like immunoreactivity was observed ipsilaterally to the operation. Contralateral deafferented tectae displayed conspicuous modifications in the normal pattern of peptide-like immunoreactivity unique to each of the substances studied. The modifications of peptide-like immunoreactivity observed varied depending both on the survival time and on the particular peptide analyzed, with either increment or diminution or disappearance--or combinations thereof--in the staining intensity of some of the peptide-positive bands in the superficial one-third (superficial neuropil) of the tectum. The onset of these changes is detectable immunocytochemically between the sixth and tenth day following deafferentation. By 2-4 weeks full expression of the long-term changes is reached with no apparent further modification up to the 99th postoperative day. The rapid onset of these phenomena suggests the existence of a previously unrecognized retinal ganglion cell terminal peptidergic contribution to the tectum and/or rapid transsynaptic effects. The former possibility is suggested by recent observations demonstrating peptide-like immunoreactivity for SP, LENK, CCK8 and BOM in the retinal stump of ligated optic nerves (Kuljis and Karten, '82b). The fact that no vertebrate retinal ganglion cells have been shown to contain any of these peptides (Brecha et al., '79; Famiglietti et al., '80; Eldred and Karten, '81; Karten et al., '82), however, argues against the possibility of a retinal terminal contribution to peptide-like immunoreactivity in the tectum and suggests that transsynaptic phenomena are involved.


KSNM60 in Non-thyroidal Radionuclide Therapy: Leaping into the Future.
This year, the Korean Society of Nuclear Medicine (KSNM) is celebrating its 60th anniversary. Treatment, as well as diagnosis, has played a very important role in the development of nuclear medicine. Since I-131 was used for thyroid therapy in 1959, other radionuclide therapy is still being used, and attempts to use new radionuclide are increasing. In this review, we briefly summarize and introduce the therapies such as radioimmunotherapy, transarterial radioembolization, radionuclide therapy for neuroendocrine tumors, peptide receptor radionuclide therapy, control of metastatic bone pain, radiation synovectomy, radionuclide brachytherapy, alpha particle therapy, and boron neutron capture therapy, which has been being attempted so far in the field of nuclear medicine.


Subscapularis function after total shoulder arthroplasty: electromyography, ultrasound, and clinical correlation.
The literature lacks electromyographic (EMG) examination of subscapularis function in the postoperative period after total shoulder arthroplasty (TSA). The primary purpose of this study was to document EMG activity of the subscapularis after TSA and to correlate it with clinical and ultrasound findings. The study included 30 patients who were at least 1 year (average, 2.1 years) from surgery, status post TSA approached through a standard subscapularis tenotomy. Patients returned for a physical examination, ultrasound evaluation, and EMG evaluation. Patients also completed postoperative surveys: the American Shoulder and Elbow Surgeons questionnaire, the Simple Shoulder Test, and the 12-Item Short Form Health Survey. The American Shoulder and Elbow Surgeons, Simple Shoulder Test, and physical 12-Item Short Form Health Survey scores improved from preoperatively to postoperatively, respectively, 45.3 to 76.8 (P = .0002), 3.9 to 9.0 (P < .0001), and 33.9 to 42.8 (P = .017). Six patients had a positive lift-off test result, and the belly-press test result was negative in all patients. Two patients had a subscapularis rupture on ultrasound. The postoperative EMG finding was normal in 15 patients; in the other 15 patients, there was evidence of chronic denervation with reinnervation changes: 30% subscapularis, 27% infraspinatus, 20% supraspinatus, 20% teres minor, and 13% rhomboids. This is the first study using a comparison EMG evaluation to document subscapularis function after TSA. EMG evaluation showed that active denervation of the subscapularis was not evident in any patient at least 1 year after TSA. However, in half of the patients, there was evidence of chronicdenervation and reinnervation changes across 5 muscle groups. We theorize that surgical exposure, traction, and the use of interscalene regional anesthesia may contribute to these unexpected EMG results.


Restless legs syndrome/Willis-Ekbom disease among patients with resistant hypertension versus stroke patients-a prospective study.
Epidemiological studies have shown an increased prevalence and incidence of hypertension as well as a higher incidence of stroke among patients suffering from RLS. The objective of this study was to estimate the prevalence of RLS among patients with resistant hypertension (RH) and compare the clinical characteristics of these patients with patients of stroke pre-existing RLS and with patients with primary RLS presenting to the Sleep clinic. Consecutive patients with RH (without any identifiable cause on extensive work up) and consecutive in-patients with stroke were enrolled over a 3-year-period. Patients with RH fulfilling revised-IRLSSG-criteria for RLS comprised group 1 and those with stroke and RLS formed group 2. These were compared with patients diagnosed to have idiopathic RLS (iRLS) (Group 3). Prevalence of RLS in groups 1 and 2 and RLS characteristics in all groups were compared. Sixteen out of 56 RH patients (29%) formed group 1 and 43 out 346 of stroke patients (12%) formed group 2, while 43 consecutive iRLS patients were included in group 3. Age was significantly higher, with male dominance in group 2. Median age at symptom onset was significantly lower in group 1. Positive family history was similar in RH and iRLS patients and was significantly less common in stroke patients. Asymmetrical/unilateral distribution of symptoms was significantly more common in stroke group, compared to RH and iRLS groups. This study demonstrated a high prevalence of RLS among patients with resistant hypertension. RLS characteristics are different from those in patients with stroke, and very similar to primary RLS.


Genotype-phenotype correlation related to lipid profile in beta-thalassemia major and intermedia in southern Iran.
Beta-thalassemia is commonly associated with lipid abnormalities. The aim of this study was to search for links between these lipid alterations and different types of β-thalassemia mutations. The study, conducted from 2009 to 2010, included 100 patients with thalassemia major (TM) and 100 with thalassemia intermedia (TI). The control group was selected from 100 age- and sex-matched healthy individuals with normal hematologic indices. Serum lipid profiles, including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG), were determined and their relationship with different covariates, including different β-globin gene mutations, was analyzed. Patients with TI had significantly lower values for TC, LDL-C, HDL-C, and LDL-C/HDL-C ratio compared with TM patients and controls (P < .001). TG was greater in TM compared with TI patients (P = .001) and healthy individuals (P = .007). Hemoglobin was positively associated with TC (P < .001), LDL-C (P = .004), and HDL-C (P = .01) in TM patients. Splenectomy correlated with greater TC (P = .006) and LDL-C (P = .01) in TI patients, but only with greater LDL-C in TM patients (P = .02). The average amounts of TC and LDL-C were lower in persons with the β(0)/β(0) mutation compared with the β(+)/β(+) group. Lower amounts of TG, TC, LDL-C, and HDL-C were seen in TI patients compared with TM patients and healthy individuals. The severity of the genotype (ie, β(0) type mutations compared with β(+) type mutations) affected the degree of reduction in serum lipids.


Unbuffered osmium staining of cell organelles: alterations induced by cell injury.
We have studied the localization of osmium reduction products to investigate the functional state of organelles as well as organelle interrelationships during cell injury. In normal hepatocytes osmium deposits of variable intensity are seen in nuclear envelope, endoplasmic reticulum. Golgi cisternae and vesicles and lysosomes. Buffering of osmium with s- collidine (pH 7.4) prevents the deposition of osmium. Reversible (30 min) and irreversible (60 min) ischemia without reflow causes no change in the pattern of osmium deposition. Irreversible ischemia followed by reflow causes decreased staining of endoplasmic reticulum (ER) and redistribution of the osmium deposits through the cytoplasm. Reversibly injured pancreatic acinar cells in cultured explants manifest a similar loss of osmium staining in the endoplasmic reticulum cisternae. The administration of antimicrotubule drugs induces an accentuation of osmium staining in localized cisternal elements of hepatocytes. These heavily stained cisternae appear to give rise to the bounding membranes of drug-induced autophagic vacuoles. Cytoplasmic organelles sequestered inside the autophagic vacuoles acquire intense staining when they begin to undergo degradation. In homogenized liver tissue all the subcellular organelles show osmium deposits. The deposits are preferentially localized along the organelle membranes. In particular the dense deposits in the ER lumen are not seen in the subcellular fractions. Phospholipase A2 (3 units/mg protein) enhances the deposition of osmium in the lumen of microsomal vesicles, whereas the presence of detergent has no such effect. Addition of EDTA to the homogenizing medium enhances the ultrastructural preservation of the subcellular fractions but has little effect on the deposition of osmium. OsO4 deposition occurs at acid pH and the intensity and pattern of the stain can be modified in vivo and in vitro. Osmium tetroxide deposition is induced at sites of membrane transformation (autophagic vacuoles) and degradation (lysosomes). Calcium influx and phospholipase activation (ischemia, tissue homogenization, phospholipase addition) enhance osmium deposition and/or influence the localization of the staining pattern.


Visual outcomes of epiretinal membrane removal after diffractive-type multifocal intraocular lens implantation.
To assess visual outcomes of epiretinal membrane (ERM) removal in multifocal intraocular lens (MIOL)-implanted eyes, according to ERM stage. Retrospective chart reviews were undertaken in patients with diffractive-type MIOL implants, each undergoing pars plana vitrectomy and ERM removal between February 2018 and November 2020 at Gyeongju St. Mary's Eye Clinic and KEYE Eye Center. Assessments focused on monocular uncorrected and corrected values of distant visual acuity (UDVA and CDVA) and uncorrected near visual acuity (UNVA) at postoperative 12 months according to the stage of ERM. The present study included a total of 49 MIOL-implanted eyes from 49 enrollees, 25 undergoing pars plana vitrectomy for ERM removal (11 eyes with Stage 2 and 14 eyes with Stage 3), and 24 acting as age-matched controls. There was a significant difference in UDVA and UNVA between control and Stage 3 ERM (UDVA; 0.01 ± 0.04 for control, and 0.07 ± 0.08 for stage 3 ERM, p = 0.035, UNVA; 0.03 ± 0.05 for control, and 0.13 ± 0.16 for Stage 3 ERM, p = 0.029). There were no significant differences in CDVA between groups (p = 0.121, ANOVA test). Eyes with Stage 3 ERM did not achieve visual acuity comparable to control eyes, suggesting the necessity of an early intervention for ERM in eyes with diffractive type MIOL. A meticulous preoperative retinal evaluation for ERM development is mandatory when planning diffractive-type MIOL implantation.


EGFR as a potent CAR T target in triple negative breast cancer brain metastases.
There is currently no curative treatment for patients diagnosed with triple-negative breast cancer brain metastases (TNBC-BM). CAR T cells hold potential for curative treatment given they retain the cytolytic activity of a T cell combined with the specificity of an antibody. In this proposal we evaluated the potential of EGFR re-directed CAR T cells as a therapeutic treatment against TNBC cells in vitro and in vivo. We leveraged a TNBC-BM tissue microarray and a large panel of TNBC cell lines and identified elevated epidermal growth factor receptor (EGFR) expression. Next, we designed a second-generation anti-EGFR CAR T construct incorporating a clinically relevant mAb806 tumor specific single-chain variable fragment (scFv) and intracellular 4-1BB costimulatory domain and CD3ζ using a lentivirus system and evaluated in vitro and in vivo anti-tumor activity. We demonstrate EGFR is enriched in TNBC-BM patient tissue after neurosurgical resection, with six of 13 brain metastases demonstrating both membranous and cytoplasmic EGFR. Eleven of 13 TNBC cell lines have EGFR surface expression ≥ 85% by flow cytometry. EGFR806 CAR T treated mice effectively eradicated TNBC-BM and enhanced mouse survival (log rank p < 0.004). Our results demonstrates anti-tumor activity of EGFR806 CAR T cells against TNBC cells in vitro and in vivo. Given EGFR806 CAR T cells are currently undergoing clinical trials in primary brain tumor patients without obvious toxicity, our results are immediately actionable against the TNBC-BM patient population.


Implementation of antiretroviral therapy (ART) in former Soviet Union countries.
Against the current global trends, in the former Soviet Union (FSU) countries HIV prevalence is on the rise. Visa-free movement across borders has facilitated migrant-associated HIV transmission within this region. Despite efforts from the governments to curtail the growing epidemic, there is still a serious need for the development of strategies that focus on high-risk behaviors and practices responsible for the continued transmission of HIV in this region. While governments of FSU countries have taken commendable steps in recent years to address hurdles at each step of the HIV care continuum, to ensure 100% antiretroviral treatment (ART) accessibility to people living with HIV (PLHIV), testing for HIV needs to be enforced widely in FSU countries. Stigma against people who inject drugs (PWID), men who have sex with men (MSM), migrants, and PLHIV need to be addressed. Finally, to avoid breaks in ART supply, FSU countries need to gain independence in funding HIV care so that the provision of ART to PLHIV is made available without interruption.


Layer-by-layer development of chitosan/alginate-based platelet-mimicking nanocapsules for augmenting doxorubicin cytotoxicity against breast cancer.
Breast carcinoma is considered one of the most invasive and life-threatening malignancies in females. Mastectomy, radiation therapy, hormone therapy and chemotherapy are the most common treatment choices for breast cancer. Doxorubicin (DOX) is one of the most regularly utilized medications in breast cancer protocols. However, DOX has showed numerous side effects including lethal cardiotoxicity. This study aims to fortify DOX cytotoxicity and lowering its side effects via its combining with the antidiabetic metformin (MET) as an adjuvant therapy, along with its effective delivery using natural platelet-rich plasma (PRP), and newly-developed PRP-mimicking nanocapsules (NCs). The PRP-mimicking NCs were fabricated via layer-by-layer (LBL) deposition of oppositely charged biodegradable and biocompatible chitosan (CS) and alginate (ALG) on a core of synthesized polystyrene nanoparticles (PS NPs) followed by removal of the PS core. Both natural PRP and PRP-mimicking NCs were loaded with DOX and MET adjuvant therapy, followed by their physicochemical characterizations including DLS, FTIR, DSC, and morphological evaluation using TEM. In-vitro drug release studies, cytotoxicity, apoptosis/necrosis, and cell cycle analysis were conducted using MCF-7 breast cancer cells. Also, an in-vivo assessment was carried out using EAC-bearing balb/c mice animal model to evaluate the effect of DOX/MET-loaded natural PRP and PRP-mimicked NCs on tumor weight, volume and growth biomarkers in addition to analyzing the immunohistopathology of the treated tissues. Results confirmed the development of CS/ALG-based PRP-mimicking NCs with a higher loading capacity of both drugs (DOX and MET) and smaller size (259.7 ± 19.3 nm) than natural PRP (489 ± 20.827 nm). Both in-vitro and in-vivo studies were in agreement and confirmed that MET synergized the anticancer activity of DOX against breast cancer. Besides, the developed LBL NCs successfully mimicked the PRP in improving the loaded drugs biological efficiency more than free drugs.


Distinct modes of TATA box utilization by the RNA polymerase III transcription machineries from budding yeast and higher plants.
The TATA box is a key upstream control element for basal tRNA gene transcription by RNA polymerase III in some eukaryotes, such as the fission yeast (Schizosaccharomyces pombe) and higher plants, but not in others such as the budding yeast (Saccharomyces cerevisiae). To gain information on this differential TATA box requirement, we examined side-by-side the in vitro transcription properties of TATA-containing and TATA-mutated plant and S. cerevisiae tDNAs in homologous in vitro transcription systems from both organisms and in a hybrid system in which yeast TBP was replaced by its plant homologue. The data support the general conclusion that specific features of the plant transcription machinery, rather than upstream region architecture per se, are responsible for the much stronger TATA box dependence of the plant system. In both systems, however, a strong influence of the TATA box on transcription start site selection was observed. This was particularly striking in the case of plant tDNAs, where TATA-rich upstream regions were found to favour the use of alternative initiation sites. Replacement of yeast TBP with its plant counterpart did not confer any general TATA box responsiveness to the yeast transcription machinery. Interactions involving components other than TBP are thus responsible for the strong TATA box requirement of plant tDNA transcription.


Neuromuscular and anaerobic performance of sprinters at maximal and supramaximal speed.
Neuromuscular and anaerobic performance was investigated in nine male sprinters who were running at maximal and supramaximal speeds. Supramaximal running was performed by a towing system. A rubber rope pulled by an electronic motor towed the runner, and the angle of draught ranged from 10 degrees to 17 degrees upward from the horizontal. All runs were filmed at 100 frames X s-1, and ground reaction forces were measured with a long force platform system. EMGs were recorded telemetrically with surface electrodes from five leg muscles. Blood lactate and oxygen debt were measured during recovery. The results indicated that in supramaximal running the increases in velocity (4.3%-4.6%) were associated with increase in stride length (P less than 0.01). Comparison of the ground reaction forces showed that in the impact phase maximal force, average force, work, and power were significantly (P less than 0.01-0.001) greater in a horizontal direction and maximal and average forces were greater (P less than 0.05-0.01) in a vertical direction compared with a preceding maximal run. There were no significant differences in EMG activity of any studied muscle between the various runs. Peak blood lactate was 27.7% (P less than 0.001) and oxygen debt 30.3% (P less than 0.01) higher after maximal than supramaximal runs. It is concluded that supramaximal running with towing horizontally and vertically simultaneously causes increases in stride length and changes are associated with a smaller energy expenditure despite the high intensity of the performance.


Human and canine leptospirosis: serological data of São Paulo City, Brazil, 2000 to 2003.
Sera from humans and dogs were tested by microscopic agglutination test. Icterohaemorrhagiae was the predominant serogroup in both groups, associated with the infestation of Rattus norvegicus.


Surveillance using capsule endoscopy is safe in post-colectomy patients with familial adenomatous polyposis: a prospective Japanese study.
The utility of capsule endoscopy (CE) for the surveillance of small intestinal lesions in familial adenomatous polyposis (FAP) patients has been reported. However, few studies have investigated the safety of CE in FAP patients who have undergone colon surgery. We aimed to assess the safety of surveillance CE in post-colectomy FAP patients and the endoscopic findings associated with small intestinal lesions. We assessed the safety of CE surveillance of small intestinal lesions in 41 FAP patients who had undergone colectomies. Forty-two CEs were performed in 41 patients at our facility from April 2012 to July 2014. CE was conducted safely and none of the capsules were retained, despite the inclusion of patients who had undergone several abdominal surgeries previously. Thirty-nine out of 42 capsules (93 %) were retrieved within the examination timeframe; hence, the retrieval rate was favorable. The findings from this study indicate that surveillance CE can be safely conducted in post-colectomy FAP patients.


Real-time wrinkle evaluation method using Visual Illusion-based image feature enhancement System.
Several advanced methods for evaluating wrinkles are currently available, however, with limitations in their application because wrinkle structures change in response to facial expressions and surrounding environments. A Visual Illusion-based image feature enhancement System (VIS) was used to develop a real-time evaluation method. This study expands the VIS application into the wrinkle evaluation method by adjusting VIS to evaluate facial wrinkles, evaluating the age-dependent wrinkles, and validating it for real-time wrinkle evaluation. Wrinkles in various Japanese men and women were evaluated using VIS and the current methods. Furthermore, the effectiveness of an eye cream containing niacinamide was evaluated before and after the 4-week treatment. VIS qualitatively detects even fine wrinkles and numerically records them without any special instrument. Moreover, VIS can be applied to moving images, revealing the effectiveness of the antiwrinkle formulation qualitatively and quantitatively even when the subjects are smiling. This paper presents an epoch-making wrinkle evaluation method that is qualitative and quantitative, with high sensitivity in real-time and relies solely on digital images without any difficulties. Therefore, these results imply that this method enables the wrinkle evaluation under real-life conditions.


Capitalizing on knowledge of hepatitis C virus neutralizing epitopes for rational vaccine design.
Hepatitis C virus infects nearly 3% of the world's population and is often referred as a silent epidemic. It is a leading cause of liver cirrhosis and hepatocellular carcinoma in endemic countries. Although antiviral drugs are now available, they are not readily accessible to marginalized social groups and developing nations that are disproportionally impacted by HCV. To stop the HCV pandemic, a vaccine is needed. Recent advances in HCV research have provided new opportunities for studying HCV neutralizing antibodies and their subsequent use for rational vaccine design. It is now recognized that neutralizing antibodies to conserved antigenic sites of the virus can cross-neutralize diverse HCV genotypes and protect against infection in vivo. Structural characterization of the neutralizing epitopes has provided valuable information for design of candidate immunogens.


Transcriptomic analysis of Rhodococcus opacus R7 grown on polyethylene by RNA-seq.
Plastic waste management has become a global issue. Polyethylene (PE) is the most abundant synthetic plastic worldwide, and one of the most resistant to biodegradation. Indeed, few bacteria can degrade polyethylene. In this paper, the transcriptomic analysis unveiled for the first time Rhodococcus opacus R7 complex genetic system based on diverse oxidoreductases for polyethylene biodegradation. The RNA-seq allowed uncovering genes putatively involved in the first step of oxidation. In-depth investigations through preliminary bioinformatic analyses and enzymatic assays on the supernatant of R7 grown in the presence of PE confirmed the activation of genes encoding laccase-like enzymes. Moreover, the transcriptomic data allowed identifying candidate genes for the further steps of short aliphatic chain oxidation including alkB gene encoding an alkane monooxygenase, cyp450 gene encoding cytochrome P450 hydroxylase, and genes encoding membrane transporters. The PE biodegradative system was also validated by FTIR analysis on R7 cells grown on polyethylene.


Physiological Monitoring in Patients with Acute Brain Injury: A Multimodal Approach.
Neurocritical care management of acute brain injury (ABI) is focused on identification, prevention, and management of secondary brain injury (SBI). Physiologic monitoring of the brain and other organ systems has a role to predict patient recovery or deterioration, guide individualized therapeutic interventions, and measure response to treatment, with the goal of improving patient outcomes. In this review, we detail how specific physiologic markers of brain injury and neuromonitoring tools are integrated and used in ABI patients to develop therapeutic approaches to prevent SBI.


Double threading through DNA: NMR structural study of a bis-naphthalene macrocycle bound to a thymine-thymine mismatch.
The macrocyclic bis-naphthalene macrocycle (2,7-BisNP), belonging to the cyclobisintercalator family of DNA ligands, recognizes T-T mismatch sites in duplex DNA with high affinity and selectivity, as evidenced by thermal denaturation experiments and NMR titrations. The binding of this macrocycle to an 11-mer DNA oligonucleotide containing a T-T mismatch was studied using NMR spectroscopy and NMR-restrained molecular modeling. The ligand forms a single type of complex with the DNA, in which one of the naphthalene rings of the ligand occupies the place of one of the mismatched thymines, which is flipped out of the duplex. The second naphthalene unit of the ligand intercalates at the A-T base pair flanking the mismatch site, leading to encapsulation of its thymine residue via double stacking. The polyammonium linking chains of the macrocycle are located in the minor and the major grooves of the oligonucleotide and participate in the stabilization of the complex by formation of hydrogen bonds with the encapsulated thymine base and the mismatched thymine remaining inside the helix. The study highlights the uniqueness of this cyclobisintercalation binding mode and its importance for recognition of DNA lesion sites by small molecules.


Translation, cross-cultural adaptation and validation of the Danish version of the Oxford hip score: Assessed against generic and disease-specific questionnaires.
The Oxford hip score (OHS) is a 12-item questionnaire designed and developed to assess function and pain from the perspective of patients who are undergoing total hip replacement (THR). The OHS has been shown to be consistent, reliable, valid and sensitive to clinical change following THR. It has been translated into different languages, but no adequately translated, adapted and validated Danish language version exists. The OHS was translated and cross-culturally adapted into Danish from the original English version, using methods based on best-practice guidelines. The translation was tested for psychometric quality in patients drawn from a cohort from the Danish Hip Arthroplasty Register (DHR). The Danish OHS had a response rate of 87.4%, no floor effect and a 19.9% ceiling effect (as expected in post-operative patients). Only 1.2% of patients had too many items missing to calculate a sum score. Construct validity was adequate and 80% of our predefined hypotheses regarding the correlation between scores on the Danish OHS and the other questionnaires were confirmed. The intraclass correlation (ICC) of the different items ranged from 0.80 to 0.95 and the average limits of agreement (LOA) ranged from -0.05 to 0.06. The Danish OHS had a high internal consistency with a Cronbach's alpha of 0.99 and an average inter-item correlation of 0.88. This Danish version of the OHS is a valid and reliable patient-reported outcome measurement instrument (PROM) with similar qualities to the original English language version.


An Evaluation of Anxiety Disorder and Emotion Regulation Difficulty in Children and Adolescents with Alopecia Areata.
The relationship between alopecia areata (AA) and emotion regulation difficulty has not yet been fully explained. The aim of the study was to investigate the levels of anxiety and emotion regulation difficulty in children diagnosed with AA. This case-control study was done in the university setting. Behavioral tests measuring anxiety and emotion regulation difficulties, and the measures assessing AA severity were applied to 32 AA patients consulted at Dermatology Clinic of Yozgat Bozok University. A control group was formed of 36 healthy children. Kolmogorov-Smirnov normality test, Mann-Whitney U test and Pearson's and Fisher's Chi-square tests and Spearman's correlation test. Evaluation was made of a total of 68 subjects (32 patients, 36 healthy subjects). The Difficulties in Emotion Regulation Scale (DERS)-total score and the DERS-clarity subscore were statistically significantly higher in the control group than in the patient group (P = 0.021, P = 0.003, respectively). No significant difference was determined between the two groups in respect of anxiety levels. No correlation was determined between disease severity and the scales. It was determined that as disease duration increased, so the DERS-non-acceptance subscale score increased, and with an increase in age, the SAI score of the AA patients increased. The DERS-impulse subscale score was seen to be statistically significantly higher in the boys with AA than in girls (P = 0.030). The results of this study showed that a visible, chronic, recurrent disease such as AA is not always seen with high psychiatric comorbidity and that together with the presence of the disease, patient age and disease duration are also important. It can be considered that AA may have been affected by the location, time and conditions of the study.


PEDF-derived peptide inhibits corneal angiogenesis by suppressing VEGF expression.
Pigment epithelium-derived factor (PEDF) a glycoprotein that belongs to the superfamily of serine protease inhibitors, has been recently shown to be the most potent inhibitor of angiogenesis in the mammalian eye. However, which active domain of PEDF protein could be involved in its anti-angiogenic properties remains unknown. Therefore, in this study, we examined which PEDF-derived synthetic peptides could inhibit corneal neovascularization induced by chemical cauterization in vivo. Rats treated with topical application of PEDF protein had 31% less corneal neovascularization at day 7 after the injury than phosphate-buffered saline (PBS)-treated rats. P5-2 and P5-3 peptides (residues 388-393 and 394-400 of PEDF protein, respectively) significantly suppressed the corneal neovascularization after chemical cauterization at day 7, and its anti-angiogenic potential was almost equal to that of full-length PEDF protein. Further, full-length PEDF protein and P5-3 peptide significantly decreased 8-hydroxy-2'-deoxyguanosine and vascular endothelial growth factor (VEGF) levels in the corneal. Our present study suggests that PEDF-derived synthetic peptide, P5-3 could inhibit the corneal neovascularization induced by chemical cauterization in rats by suppressing VEGF expression via its anti-oxidative properties.


[Development of adenocarcinoma in a retrorectal pre-sacrococcygeal hamartoma].
Among the different pathologic structures of the presacrococcygeal space retrorectal cystic hamartomas are uncommon lesions. These cysts are most likely derived from remnants of the embryonic tailgut although an association to teratomas may exist. We describe the clinicopathologic features of a retrorectal cystic hematoma with malignant transformation in a 60 year old female patient. The literature is reviewed and etiology, diagnosis and operative management are discussed.


The dual nature of the nucleolus.
The nucleolus is best known for housing the highly ordered assembly line that produces ribosomal subunits. The >100 ribosome assembly factors in the nucleolus are thought to cycle between two states: an operative state (when integrated into subunit assembly intermediates) and a latent state (upon release from intermediates). Although it has become commonplace to refer to the nucleolus as "being a multilayered condensate," and this may be accurate for latent factors, there is little reason to think that such assertions pertain to the operative state of assembly factors.


Guidelines for cognitive behavioral training within doctoral psychology programs in the United States: report of the Inter-organizational Task Force on Cognitive and Behavioral Psychology Doctoral Education.
The Association for Behavioral and Cognitive Therapies initiated an interorganizational task force to develop guidelines for integrated education and training in cognitive and behavioral psychology at the doctoral level in the United States. Fifteen task force members representing 16 professional associations participated in a year-long series of conferences, and developed a consensus on optimal doctoral education and training in cognitive and behavioral psychology. The recommendations assume solid foundational training that is typical within applied psychology areas such as clinical and counseling psychology programs located in the United States. This article details the background, assumptions, and resulting recommendations specific to doctoral education and training in cognitive and behavioral psychology, including competencies expected in the areas of ethics, research, and practice.


CDH1 gene polymorphisms, smoking, Helicobacter pylori infection and the risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST).
Despite declining incidence rates, gastric cancer (GC) is a major cause of death worldwide. E-Cadherin is an adhesion molecule that is thought to be involved in GC. Germline mutations in the E-Cadherin gene (CDH1) have been identified in hereditary diffuse GC. Also, a promoter polymorphism at position -160 C/A has been suggested to lead to transcriptional down regulation and has been shown to affect GC risk in some studies. However, very little information exists on the GC risk association of other CDH1 polymorphisms and it is unclear whether any associations may be different by GC anatomical sites or histological types. Thus, a case-control study (cases=245/controls=950) nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort was conducted to assess the GC risk association of eight CDH1 gene polymorphisms. None of the CDH1 polymorphisms or haplotypes analysed were associated with GC risk and no differences of effect were observed by Helicobacter pylori infection status. However, three CDH1 polymorphisms in the same haplotype block, including the CDH1-160C/A, interacted with smoking to increase GC risk in smokers but not in never smokers. These findings should be confirmed in larger independent studies.


Oxidative stress promotes SIRT1 recruitment to the GADD34/PP1α complex to activate its deacetylase function.
Phosphorylation of the eukaryotic translation initiation factor, eIF2α, by stress-activated protein kinases and dephosphorylation by the growth arrest and DNA damage-inducible protein (GADD34)-containing phosphatase is a central node in the integrated stress response. Mass spectrometry demonstrated GADD34 acetylation at multiple lysines. Substituting K315 and K322 with alanines or glutamines did not impair GADD34's ability to recruit protein phosphatase 1α (PP1α) or eIF2α, suggesting that GADD34 acetylation did not modulate eIF2α phosphatase activity. Arsenite (Ars)-induced oxidative stress increased cellular GADD34 levels and enhanced Sirtuin 1 (SIRT1) recruitment to assemble a cytoplasmic complex containing GADD34, PP1α, eIF2α and SIRT1. Induction of GADD34 in WT MEFs paralleled the dephosphorylation of eIF2α (phosphoserine-51) and SIRT1 (phosphoserine-47). By comparison, eIF2α and SIRT1 were persistently phosphorylated in Ars-treated GADD34-/- MEFs. Expressing WT GADD34, but not a mutant unable to bind PP1α in GADD34-/- MEFs restored both eIF2α and SIRT1 dephosphorylation. SIRT1 dephosphorylation increased its deacetylase activity, measured in vitro and in cells. Loss of function of GADD34 or SIRT1 enhanced cellular p-eIF2α levels and attenuated cell death following Ars exposure. These results highlighted a novel role for the GADD34/PP1α complex in coordinating the dephosphorylation and reactivation of eIF2α and SIRT1 to determine cell fate following oxidative stress.


Scintigraphic detection of gynaecological tumours by 99mTc-HSA blood pool imaging.
Three cases of scintigraphic visualization of gynaecological tumours by 99mTc-HSA blood pool imaging are presented, i.e. one case of fibrothecoma ("cold" area visualization) and two cases of fibromyoma ("hot" area visualization). It is suggested that this technique may be useful in the preoperative evaluation of gynaecological tumours and their vascularity.


A high throughput screening system of coils for ELF magnetic fields experiments: proof of concept on the proliferation of cancer cell lines.
It has been demonstrated that relatively small variations of the parameters of exposure to extremely low frequency magnetic fields (ELF-MF) can change significantly the outcome of experiments. Hence, either in trying to elucidate if these fields are carcinogenic, or in exploring their possible therapeutic use, it is desirable to screen through as many different exposures as possible. The purpose of this work is to provide a proof of concept of how a recently reported system of coils allows testing different field exposures, in a single experiment. Using a novel exposure system, we subjected a glioblastoma cancer cell line (U251) to three different time modulations of an ELF-MF at 60 different combinations of the alternated current (AC) and direct current (DC) components of the field. One of those three time modulations was also tested on another cell line, MDA-MB-231 (breast cancer). After exposure, proliferation was assessed by colorimetric assays. For the U251 cells, a total of 180 different exposures were tested in three different experiments. Depending on exposure modulation and AC field intensity (but, remarkably, not on DC intensity), we found the three possible outcomes: increase (14.3% above control, p < 0.01), decrease (16.6% below control, p < 0.001), and also no-effect on proliferation with respect to control. Only the time modulation that inhibited proliferation of U251 was also tested on MDA-MB-231 cells which, in contrast, showed no alteration of their proliferation on any of the 60 AC/DC field combinations tested. We demonstrated, for the first time, the use of a novel system of coils for magnetobiology research, which allowed us to find that differences of only a few μT resulted in statistically different results. Not only does our study demonstrate the relevance of the time modulation and the importance of finely sweeping through the AC and DC amplitudes, but also, and most importantly, provides a proof of concept of a system that sensibly reduces the time and costs of screening.


Impact of youth and caregiver worries about treatment on therapeutic process factors and posttreatment outcomes.
To examine the impact of youth- and caregiver-reported pretreatment worries about treatment (i.e., concerns about the effect of, perceptions of, or aspects involved in treatment) before cognitive behavioral therapy for anxiety on (1) clinician-rated therapeutic process factors (i.e., client engagement, client-therapist alliance, content mastery, and homework completion) and symptom change (i.e., improvement, anxiety severity) assessed throughout treatment and (2) independent evaluator-rated posttreatment outcomes (i.e., response, remission, and functional impairment). Participants were 128 youth, aged 7-17 years, who sought treatment for a principal anxiety disorder, and their primary caregiver. Multilevel models were estimated to examine the relationship between worries about treatment and the set of therapeutic factors. Regression models examined the relationship between worries about treatment and posttreatment outcomes. Results indicated that greater youth-reported worries about treatment flattened/lessened improvement trajectories throughout treatment and had a positive association with higher anxiety severity and lower content mastery. Greater caregiver-reported worries about treatment were associated with greater homework completion, client engagement, and content mastery throughout treatment. Youth- and caregiver-reports of worries about treatment did not impact independent evaluator-rated posttreatment outcomes. Findings support the notion that worries about treatment do not prevent youth from achieving favorable posttreatment outcomes, but do impact various therapeutic factors differentially across youth and caregiver report (e.g., content mastery, client engagement, and homework completion). The value of addressing worries about treatment at the start of therapy is discussed.


Polymorphism of esterase 11 in Mus musculus, a further esterase locus on chromosome 8.
A further esterase, esterase 11, which exhibits a polymorphism detectable by electrophoresis, has been observed in the house mouse, Mus musculus. In 15 inbred strains and two outbred strains, the ES-11A phenotype has been found, composed of two bands of enzyme activity of greater anodal electrophoretic mobility than the two bands of the ES-11B phenotype found in one inbred strain, one wild stock, and 101 wild mice. In F1 hybrids (IS/Cam X C57BL/Gr), the phenotype shown corresponds to a mixture of the two parental phenotypes. In backcrosses, ES-11 segregates as an autosomal gene, designated Es-11, closely linked to Es-2 and Es-5 on chromosome 8.


Analysis of Helicobacter pylori and nonsteroidal anti-inflammatory drug-induced gastric epithelial injury.
Helicobacter pylori and nonsteroidal anti-inflammatory drugs (NSAIDs) are important factors in gastric mucosal injury. However, the relationship between H. pylori and NSAID-related gastroduodenal mucosal injury has not been clarified. To determine the role of H. pylori in NSAID-induced gastric mucosal injury and to examine the effects of H. pylori, indomethacin and sofalcone on gastric epithelial cells in culture, as a useful model to study gastric mucosal injury. In addition, we studied the effect of sofalcone, a gastric mucosal protection agent, on H. pylori and NSAID-induced gastric mucosal injury. Cytotoxic and noncytotoxic strains of H. pylori were used, each with an inoculum of 10(7) cfu/mL. The effect on the growth of RGM-1 cells (a rat gastric epithelial cell line) was studied by MTT assay, and levels of prostaglandin E2 in culture supernatants were measured by EIA. Both cytotoxic and noncytotoxic strains of H. pylori tended to induce cell injury in RGM-1 cells at 48 h after inoculation. Indomethacin alone induced gastric epithelial injury in a dose-dependent manner, but did not augment cell injury induced by H. pylori. In addition, sofalcone (10(-5) mol/L) showed a suppressive effect on indomethacin-induced gastric epithelial injury. These findings indicate that indomethacin induces gastric mucosal injury regardless of H. pylori infection, and suggests that sofalcone may be a useful drug in the treatment of NSAID-induced mucosal injury.


A `one-two punch' therapy strategy to target chemoresistance in estrogen receptor positive breast cancer.
Cancer cell phenotypes evolve during a tumor's treatment. In some cases, tumor cells acquire cancer stem cell-like (CSL) traits such as resistance to chemotherapy and diminished differentiation; therefore, targeting these cells may be therapeutically beneficial. In this study we show that in progressive estrogen receptor positive (ER+) metastatic breast cancer tumors, resistant subclones that emerge following chemotherapy have increased CSL abundance. Further, in vitro organoid growth of ER+ patient cancer cells also shows that chemotherapy treatment leads to increased abundance of ALDH+/CD44+ CSL cells. Chemotherapy induced CSL abundance is blocked by treatment with a pan-HDAC inhibitor, belinostat. Belinostat treatment diminished both mammosphere formation and size following chemotherapy, indicating a decrease in progenitor CSL traits. HDAC inhibitors specific to class IIa (HDAC4, HDAC5) and IIb (HDAC6) were shown to primarily reverse the chemo-resistant CSL state. Single-cell RNA sequencing analysis with patient samples showed that HDAC targets and MYC signaling were promoted by chemotherapy and inhibited upon HDAC inhibitor treatment. In summary, HDAC inhibition can block chemotherapy-induced drug resistant phenotypes with 'one-two punch' strategy in refractory breast cancer cells.


Polyion complex micelles as vectors in gene therapy--pharmacokinetics and in vivo gene transfer.
To establish non-viral gene delivery systems for intravenous administration, complexes of DNA and block copolymer consisting of poly-L-lysine and poly(ethylene glycol) were tested in in vivo turnover studies. The polyion complex micelles have self-assembling core-shell structures, yielding spherical nano-particles with small absolute values of zeta-potential. Southern blot analysis showed that supercoiled DNA was observed for 30 min and open circular or linear DNA was seen for 3 h after intravenous administration of PIC micelles having the charge ratios of 1:4 and PLL length of 48 mer. The PIC micelles with shorter PLL length showed lower stability in the blood stream suggesting that DNA is able to persist as an intact molecule in the blood stream using this system. Though having no ligands, PIC micelles with charge ratios of 1:2 and 1:4 transfected efficiently into HepG2 cells. Preincubation with free copolymer inhibited expression of the reporter gene, suggesting that adsorption of block copolymer to the cell surface blocked the interaction site of the PIC micelles. When the PIC micelles were injected via supramesenteric vein, expression of the gene was observed only in the liver and was sustained for 3 days. It was suggested that this gene delivery system is intrinsically efficient.


Stroke and Behavior.
Most patients who have endured a stroke sustain behavioral changes, although in many instances these effects can be subtle. Although behavioral changes after a stroke tend to improve, they may persist and have serious effects on daily living activities. This article reviews the more familiar behavioral changes that follow stroke, as well as exotic, less often encountered manifestations. This article acquaints the clinician with the diversity of the behavioral effects of stroke, along with methods for their assessment and management.


Papillomatous digital dermatitis in Chilean dairies and evaluation of a screening method.
Outbreaks of papillomatous digital dermatitis (PDD) have been reported from many countries, but there is little information on prevalence and geographic distribution of the disease. Our objectives were to describe prevalence of PDD on dairies belonging to the two main dairy-producer associations in Chile, and to evaluate a milking-parlor screening method for detection of PDD in dairy cows. First, a self-administered questionnaire was sent to all 214 association dairy managers. Seventy percent of the 119 respondents had observed PDD on their dairies. About 83% of the 63 responding managers had first seen PDD during the previous 10 years. Subsequently, a random sample of 43 dairies stratified by association was selected from the total 214 for PDD screening. During milking, we inspected cows' feet for PDD lesions; 91% of dairies had cows affected by PDD; median PDD prevalence for milking cows in dairies was 6.1%. Finally, in one dairy, PDD screening at the parlor was compared to PDD diagnosis by inspecting restrained cows in a chute. The screening method had a sensitivity of 0.72, and a specificity of 0.99. This study demonstrated that PDD was widespread on study dairies in Chile. The screening test presented can be used as a cost efficient method to estimate prevalence of PDD either on individual dairies or in large-scale surveys.


SkullEngine: A Multi-Stage CNN Framework for Collaborative CBCT Image Segmentation and Landmark Detection.
Accurate bone segmentation and landmark detection are two essential preparation tasks in computer-aided surgical planning for patients with craniomaxillofacial (CMF) deformities. Surgeons typically have to complete the two tasks manually, spending ~12 hours for each set of CBCT or ~5 hours for CT. To tackle these problems, we propose a multi-stage coarse-to-fine CNN-based framework, called SkullEngine, for high-resolution segmentation and large-scale landmark detection through a collaborative, integrated, and scalable JSD model and three segmentation and landmark detection refinement models. We evaluated our framework on a clinical dataset consisting of 170 CBCT/CT images for the task of segmenting 2 bones (midface and mandible) and detecting 175 clinically common landmarks on bones, teeth, and soft tissues. Experimental results show that SkullEngine significantly improves segmentation quality, especially in regions where the bone is thin. In addition, SkullEngine also efficiently and accurately detect all of the 175 landmarks. Both tasks were completed simultaneously within 3 minutes regardless of CBCT or CT with high segmentation quality. Currently, SkullEngine has been integrated into a clinical workflow to further evaluate its clinical efficiency.


Tubulin Dimer Reversible Dissociation: AFFINITY, KINETICS, AND DEMONSTRATION OF A STABLE MONOMER.
Tubulins are evolutionarily conserved proteins that reversibly polymerize and direct intracellular traffic. Of the tubulin family only αβ-tubulin forms stable dimers. We investigated the monomer-dimer equilibrium of rat brain αβ-tubulin using analytical ultracentrifugation and fluorescence anisotropy, observing tubulin in virtually fully monomeric and dimeric states. Monomeric tubulin was stable for a few hours and exchanged into preformed dimers, demonstrating reversibility of dimer dissociation. Global analysis combining sedimentation velocity and fluorescence anisotropy yielded Kd = 84 (54-123) nm Dimer dissociation kinetics were measured by analyzing the shape of the sedimentation boundary and by the relaxation of fluorescence anisotropy following rapid dilution of labeled tubulin, yielding koff in the range 10(-3)-10(-2) s(-1) Thus, tubulin dimers reversibly dissociate with moderately fast kinetics. Monomer-monomer association is much less sensitive than dimer-dimer association to solution changes (GTP/GDP, urea, and trimethylamine oxide).


Cell type-specific distribution of cathepsin B and D immunoreactivity within the rabbit retina.
The cellular localization of cathepsin B and D immunoreactivity was demonstrated at the light microscopic level in the retina of adult rabbits by use of the peroxidase-antiperoxidase technique. Antisera were raised against rat liver enzymes. Whereas cathepsin D immunoreactivity was confined to Müller (glial) cells, cathepsin B was demonstrated in some, but not all, neuronal cell types. It is proposed that the two enzymes might carry different functions within the neuronal versus glial compartment.


Effect of exposure factors on image quality in screening mammography.
The aim of this research was to study the effect of exposure factors on image quality for digital screening mammography units in Kuwait which use Tungsten (W) targets with Rhodium (Rh) and Silver (Ag) as filters. Mammography Accreditation Phantom Model 015 was imaged using a Hologic Selenia Digital mammography unit with W targets and Rh and Ag filters. Four images, each at 26, 28, 30, and 32 kVp, were obtained using each target-filter combination (W/Rh and W/Ag). The images were evaluated by five senior technologists for the number of specks, fibers and masses visible on each image. Statistical analysis was carried out using non-parametric tests at p = 0.05 level. There were significant changes in the visibility of fibers and specks between different kVp values with W/Rh (p < 0.001). However, with W/Ag combination, significant differences were observed in the fibers only (p < 0.001). Among the kVp values used, 28 kV emerged as the optimal value. Comparison of images obtained with the two filter materials, led to significant differences in the visibility of fibers and specks (p < 0.008). At 32 kVp, there were significant differences in the visibility of specks only (p < 0.008). A W/Rh target-filter combination provides better image quality than that provided by W/Ag. In particular, 30 and 32 kVp X-ray beams produce higher quality images than the lower kV values.


Evaluation of efficacy and safety markers in a phase II study of metastatic colorectal cancer treated with aflibercept in the first-line setting.
Aflibercept (ziv-aflibercept) is an anti-angiogenic agent recently approved in combination with FOLFIRI for the treatment of metastatic colorectal cancer (mCRC) patients previously treated with oxaliplatin. Despite heterogeneity in response to aflibercept, no biomarkers for efficacy or adverse effects have been identified. Here we present biomarker data from the randomised phase II AFFIRM trial assessing aflibercept in combination with mFOLFOX6 first line in mCRC. Ninety-six somatic mutations in key oncogenic drivers of mCRC and 133 common single-nucleotide polymorphisms (SNPs) in vascular endothelial growth factor (VEGF) pathway genes were analysed, and 27 plasma markers measured at baseline, during and after treatment. We assessed correlations of these three classes of biomarkers with progression-free survival (PFS) and adverse events (AEs). Somatic mutations identified in KRAS, BRAF, NRAS, PIK3CA and PIK3R1 did not significantly correlate with PFS (multiple testing-adjusted false discovery rate (FDR) or multiple testing-adjusted FDR>0.3). None of the individual SNPs correlated with PFS (multiple testing-adjusted FDR>0.22), but at the gene level variability in VEGFB significantly correlated with PFS (multiple testing-adjusted FDR=0.0423). Although none of the plasma markers measured at baseline significantly correlated with PFS, high levels of circulating IL8 at baseline together with increased levels of IL8 during treatment were significantly associated with reduced PFS (multiple testing-adjusted FDR=0.0478). No association was found between biomarkers and AEs. This represents the first biomarker study in mCRC treated with aflibercept. High IL8 plasma levels at baseline and subsequent increases in IL8 were associated with worse PFS, suggesting that IL8 may act as a potentially predictive biomarker of aflibercept treatment outcome.


Therapeutic dilemmas in prostate cancer: justification for watchful waiting.
Despite the large numbers of elderly men known to harbour pathological evidence of prostate cancer and evidence from observational studies suggesting the prolonged time course of such disease, conservative management of such patients has not enjoyed the widespread support of urologists, particularly in the USA, where monitoring of patients is often dismissed as 'intentional neglect' rather than 'watchful waiting'. This paper outlines the rationale and principles underlying expectant treatment of patients with prostate cancer.


The Association between Major Dietary Pattern and Low Muscle Mass in Korean Middle-Aged and Elderly Populations: Based on the Korea National Health and Nutrition Examination Survey.
Reduced skeletal muscle mass in older populations is independently associated with functional impairment and disability, resulting in increased risk of mortality and various comorbidities. This study aimed to examine the association between major dietary pattern and low muscle mass among Korean middle-aged and elderly populations. A total of 8136 participants aged ≥50 years were included from a cross-sectional study based on the 2008-2011 Korea National Health and Nutrition Examination Survey. The following four distinct dietary patterns were derived using factor analysis: "Condiment, vegetables, and meats"; "wheat flour, bread, fruits, milk, and dairy products"; "white rice, fish, and seaweeds"; and "whole grain, bean products, and kimchi". A higher "white rice, fish, and seaweeds" pattern score was associated with a lower prevalence of low muscle mass in both men and women, whereas a higher "condiment, vegetables, and meats" pattern score was associated with a higher prevalence of low muscle mass in men. A dietary pattern based on white rice, fish, and seaweeds can be helpful in protecting against loss of skeletal muscle mass in Korean middle-aged and elderly populations. Future research is paramount to confirm the causal association between dietary pattern and the risk of low muscle mass.


A curious isolated cystic lesion of the membranous atrioventricular septum.
We present the case of an isolated cystic lesion of the atrioventricular component of the membranous septum of unclear aetiology, but responsible for cardiomegaly and benign disturbances of cardiac rhythm. As far as we are aware, this type of lesion has not previously been documented.


Fronto-limbic circuitry in euthymic bipolar disorder: evidence for prefrontal hyperactivation.
Functional magnetic resonance imaging (fMRI) studies of bipolar disorder have revealed fronto-limbic abnormalities in patients during manic and depressive episodes. However, relatively few studies have examined neural activity during euthymia, leaving unanswered questions concerning the impact of mood state on activity in these brain regions. In the present study, we examined 15 remitted bipolar type I patients and 16 demographically matched healthy comparison subjects during performance on an affective face-matching task previously shown to elicit amygdala hyperactivation and prefrontal hypoactivation in manic relative to healthy subjects. In our euthymic sample, amygdala activation did not differ from controls. However, bipolar patients showed hyperactivation in inferior prefrontal cortical regions compared with controls, a finding that contrasts with the hypoactivation previously reported in this region in manic patients. Given the reciprocal relationship between the prefrontal cortex and limbic structures, we propose state-related amygdala activity, similar to that of healthy controls, may be associated with prefrontal hyperactivation when bipolar patients are asymptomatic.


Cytotoxin-producing Escherichia coli and the hemolytic uremic syndrome.
Recently, a new class of diarrhea-associated Escherichia coli has been linked to the hemolytic uremic syndrome. The organisms included in this group produce cell-damaging toxins (cytotoxins) related to Shigatoxin made by S. dysenteriae 1. The most common pathogen in this group is E. coli O157:H7.


Efficacy and safety of vedolizumab in the treatment of ulcerative colitis.
Integrins play a crucial role in the development and maintenance of the inflammatory process in patients with inflammatory bowel disease. Vedolizumab is a humanized monoclonal antibody with a predominantly gastrointestinal effect. It specifically inhibits leukocyte integrin α4β7, thus preventing its interaction with mucosal vascular addressin cell adhesion molecule 1(MAdCAM-1), which is involved in the migration of lymphocytes from the blood stream to the intestinal tissue. Vedolizumab is indicated in the treatment of moderate to severe active Crohn's disease and ulcerative colitis in adult patients with poor response, loss of response, or intolerance to conventional treatment or to tumour necrosis factor alpha (TNF-α) antagonists. This review presents the most relevant clinical outcomes of vedolizumab in the treatment of patients with ulcerative colitis.


Looking backwards from outcome to exposure to assess cancer latency.
Assessing time relationships in cancer epidemiology involves linking exposure and cancer incidence or mortality on a time scale. The traditional approach is to make some exposure criterion the referent point, such as date of first exposure. However, the time relationships between exposure and cancer may also be usefully explored using the date of diagnosis (or death) as the referent point in time. This has been accomplished to date in industry-based case-control studies by estimating the etiologic fraction among ever exposed cases for years prior to death from cancer, and in the serially additive expected dose (SAED) model by estimating excess case exposure dose for each year prior to cancer death. Each of these measures assesses exposure in time windows (of arbitrary width) prior to cancer death or diagnosis. Both measures are mathematically related (by constants) to a measure of the fraction of excess case exposure dose achieved in each time window, where "excess" means beyond that expected on the basis of non-cases or controls. This particular measure, the retrospective excess exposure fraction (REEF) in time windows, may be valuable in exploring time relationships between exposure and cancer. It is concluded that retrospective measures between cancer occurrence and exposure warrant further attention to maximize the informativeness of cancer epidemiology studies.


Acute procedural complications and in-hospital events after percutaneous coronary interventions: eptifibatide versus abciximab.
Glycoprotein IIb/IIIa antagonists reduce peri-angioplasty ischemic complications and improve in-hospital outcome in patients undergoing percutaneous coronary interventions (PCI). Prior studies have demonstrated favorable results with both eptifibatide and abciximab. The purpose of this study was to assess whether there are any differences in rates of acute procedural complications and in-hospital events with the use of these two agents. A retrospective review of 359 elective PCIs from June 1998 to August 2000 identified 152 PCIs treated with eptifibatide (bolus 180 microg/kg, infusion 2 microg/kg/min for 12-48 h) and 205 PCIs treated with abciximab (bolus 0.25 mg/kg, infusion 10 microg/min for 12 h). All patients received IIb/IIIa antagonists at the initiation of the intervention. The clinical demographics, the angiographic morphology, the indications, and the procedural details were similar in both groups. In the eptifibatide group, the maximum ACT was lower (235+/-45 vs. 253+/-40, P<.0001). The incidence of major procedural and in-hospital events was compared. Eptifibatide and abciximab had similar rates of major complications (death or myocardial infarction) (1.4% vs. 2.9%), repeat PTCA (3.4% vs. 1.9%), and major bleeding (3.3% vs. 4.3%). Eptifibatide is comparable to abciximab in regards to acute procedural complications and in-hospital events after PCI.


Factors associated with bone mineral density in adults: a cross-sectional population-based study.
This study aimed to analyze the association between lumbar spine, femoral neck, total hip bone mineral density (biophysical bone health assessment parameter), and sociodemographic, anthropometric, behavioral, and health condition factors in Brazilian adults. This is a cross-sectional, population-based study performed with individuals of both genders, aged between 20 and 59 (n=701). The dependent variables were evaluated by Dual Energy X-ray Absorptiometry. The independent variables were evaluated through a questionnaire, anthropometric evaluation and blood collection. The association between bone mineral density and the independent variables was evaluated by linear regression analysis. All analyses were stratified by gender. Men presented higher bone mineral density than women. Bone mineral density was inversely associated with age range and directly associated with nutritional status in both genders and in the three bone sites analyzed. In addition, 25 Hydroxyvitamin D deficient status among men and contraceptive use among women were associated with lower bone mineral density, and a significant association was only found with lumbar spine bone mineral density in women. The factors associated with bone health among men were age, skin color, nutritional status, and vitamin D status. For women, the associated factors with bone health were age, skin color, nutritional status and contraceptive use.


The effect of selenium supplementation on sonographic findings of salivary glands in papillary thyroid cancer (PTC) patients treated with radioactive iodine: study protocol for a double-blind, randomized, placebo-controlled clinical trial.
Thyroid cancer is a very damaging disease. The most common treatment for this disease includes thyroidectomy and then using radioactive iodine (RAI). RAI has many side effects, including a decrease in salivary secretions, followed by dry mouth and oral and dental injuries, as well as increased inflammation and oxidative stress. Selenium can be effective in these patients by improving inflammation and oxidative stress and by modulating salivary secretions. So far, only one clinical trial has investigated the effect of selenium on thyroid cancer patients treated with radioiodine therapy (RIT) conducted on 16 patients; considering the importance of this issue, to show the potential efficacy of selenium in these patients, more high-quality trials with a larger sample size are warranted. This is a parallel double-blind randomized controlled clinical trial that includes 60 patients aged 20 to 65 years with papillary thyroid cancer (PTC) treated with RAI and will be conducted in Seyyed al-Shohada Center, an academic center for referral of patients to receive iodine, Isfahan, Iran. Thirty patients will receive 200 µg of selenium for 10 days (3 days before to 6 days after RAI treatment) and another 30 patients will receive a placebo for the same period. Sonographic findings of major salivary glands, salivary secretions, and sense of taste will be evaluated before and 6 months after 10-day supplementation. Due to its anti-inflammatory and antioxidant effects, as well as improving salivary secretions, selenium may improve the symptoms of thyroid cancer treated with radioactive iodine. In past studies, selenium consumption has not reduced the therapeutic effects of radiation therapy, and at a dose of 300 to 500 μg/day, it has not had any significant side effects in many types of cancer under radiation therapy. Iranian Registry of Clinical Trials IRCT20201129049534N6 . Registered on 16 September 2021.


Time-dependent cellular morphogenesis and matrix stiffening in proteolytically responsive hydrogels.
Mesenchymal stromal cells residing in proteolytically responsive hydrogel scaffolds were subjected to changes in mechanical properties associated with their own three-dimensional (3-D) morphogenesis. In order to investigate this relationship the current study documents the transient degradation and restructuring of fibroblasts seeded in hydrogel scaffolds undergoing active cell-mediated reorganization over 7days in culture. A semi-synthetic proteolytically degradable polyethylene glycol-fibrinogen (PF) hydrogel matrix and neonatal human dermal fibroblasts (NHDF) were used. Rheology (in situ and ex situ) measured stiffening of the gels and confocal laser scanning microscopy (CLSM) measured cell morphogenesis within the gels. The assumption that the matrix modulus systematically decreases as cells locally begin to enzymatically disassemble the PF hydrogel to become spindled in the material was not supported by the bulk mechanical property measurements. Instead, the PF hydrogels exhibited cell-mediated stiffening concurrent with their dynamic morphogenesis, as indicated by a four-fold increase in storage modulus after 1week in culture. Fibrin hydrogels, which were used as the control biomaterial, proved similarly adaptive to cell-mediated remodeling only in the presence of the exogenous serine protease inhibitor aprotinin. Acellular and non-viable hydrogels also served as control groups to verify that transient matrix remodeling was entirely associated with cell-mediated events, including collagen deposition, cell-mediated proteolysis, and the formation of multicellular networks within the hydrogel constructs. The fact that cell network formation and collagen deposition both paralleled transient stiffening of the PF hydrogels, further reinforces the notion that cells actively balance between proteolysis and ECM synthesis when remodeling proteolytically responsive hydrogel scaffolds.


Orally active indole N-oxide PDE4 inhibitors.
This communication describes the synthesis and in vitro and in vivo evaluation of a novel potent series of phosphodiesterase type (IV) (PDE4) inhibitors. Several of the compounds presented possess low nanomolar IC50's for PDE4 inhibition and excellent in vivo activity for inhibition of TNF-alpha levels in LPS challenged mice (mouse endotoxemia model). Emesis studies (dog) and efficacy in a SCW arthritis model for the most potent PDE4 inhibitors are presented.


Total shoulder arthroplasty: long-term survivorship, functional outcome, and quality of life.
This study examines long-term outcomes of total shoulder arthroplasty (TSA) via survivorship analysis, patient questionnaires, and minimum 10-year physical examinations. The study group consisted of 320 consecutive TSAs performed in 267 patients between 1974 and 1988. Diagnoses included rheumatoid arthritis (69%), osteoarthritis (22%), and juvenile rheumatoid arthritis (4.7%). Minimum 10-year physical examination follow-up was obtained on a subset of 72 TSAs at a mean (+/- SD) of 14.0 +/- 2.7 years. A Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire was obtained from 80 patients with 103 TSAs at a mean of 15.4 +/- 3.4 years after the index procedure (range, 10.4-23.2 years). Kaplan-Meier survivorship rates with revision as the endpoint at 5, 10, 15, and 20 years were 98%, 93%, 88%, and 85%, respectively. Of the shoulders, 22 (6.9%) required a revision, most commonly for loosening of one or both components (15 shoulders). Dislocation occurred earlier than other causes of revision or complication (P < .05, analysis of variance). Minimum 10-year physical examination follow-up revealed lasting, significant improvements in range of motion and strength. The patients' subjective assessments of TSA were favorable in that 92% felt that their shoulder was "much better" or "better" after TSA. The mean DASH score was 49 +/- 25; no significant differences were found among diagnoses. Long-term analysis of the Neer-type TSA revealed survivorship rates comparable to other joint replacements. The significant improvements in relief of pain, shoulder range of motion, and strength are associated with a high degree of patient satisfaction.


Levofloxacin rescues mice from lethal intra-nasal infections with virulent Francisella tularensis and induces immunity and production of protective antibody.
The ability to protect mice against respiratory infections with virulent Francisella tularensis has been problematic and the role of antibody-versus-cell-mediated immunity controversial. In this study, we tested the hypothesis that protective immunity can develop in mice that were given antibiotic therapy following infection via the respiratory tract with F. tularensis SCHU S4. We show that mice infected with a lethal dose of SCHU S4, via an intra-nasal challenge, could be protected with levofloxacin treatment. This protection was evident even when levofloxacin treatment was delayed 72h post-infection. At early time points after levofloxacin treatment, significant numbers of bacteria could be recovered from the lungs and spleens of mice, which was followed by a dramatic disappearance of bacteria from these tissues. Mice successfully treated with levofloxacin were later shown to be almost completely resistant to re-challenge with SCHU S4 by the intra-nasal route. Serum antibody appeared to play an important role in this immunity. Normal mice, when given sera from animals protected by levofloxacin treatment, were solidly protected from a lethal intra-nasal challenge with SCHU S4. The protective antiserum contained high titers of SCHU S4-specific IgG2a, indicating that a strong Th1 response was induced following levofloxacin treatment. Thus, this study describes a potentially valuable animal model for furthering our understanding of respiratory tularemia and provides suggestive evidence that antibody can protect against respiratory infections with virulent F. tularensis.


[Application of motorized intramedullary lengthening nails in skeletally immature patients : Indications and limitations].
Limb lengthening and deformity correction with motorized intramedullary lengthening nails is a more comfortable and equally safe procedure than the use of external fixators. While this treatment is a well-established method in adults, intramedullary nailing for skeletally immature patients remains a challenge and is the focus of current clinical investigations. Elucidation of the indications for the application of femoral and tibial lengthening nails in skeletally immature patients, presentation of essential characteristics and limitations of the treatment. Treatment of skeletally immature patients up to 16 years old who had a lengthening nail inserted was retrospectively clinically and radiologically evaluated (2016-2018). A total of 60 procedures were performed on 54 patients. Mean age at the time of surgery was 13.6 years and the mean follow-up time was 10 months. Different nailing approaches were used: antegrade femoral (n = 42), retrograde femoral (n = 10) and antegrade tibial (n = 8). The average amount of lengthening was 45 mm. In 58 of the 60 cases (96.7%) the desired amount of lengthening was achieved, while 2 patients experienced complications that required interruption of the treatment. None of the patients developed growth disorders associated with the nailing approach. Different approaches for intramedullary lengthening nails can be used in children and adolescents to correct leg length discrepancy with or without concomitant deformities. The treatment is limited by the size of the available nails, the residual growth and extent of the deformity. Larger trials will be needed to further validate the application of lengthening nails in skeletally immature patients.


Eating patterns of community-dwelling older adults: the Cardiovascular Health Study.
We analyzed eating patterns of 4643 adults (1988 men and 2655 women) aged 65 years and older at the time of their enrollment in the Cardiovascular Health Study. Diet was assessed with a qualitative, picture-sort food frequency questionnaire along with supplemental questions on other eating pattern variables. Consumption of high fat foods and low fiber foods was more frequent in older participants, men, minorities, and persons with body mass index > or = 30 kg/m2 and less common among persons who reported following self-prescribed or medically prescribed special diets. Few associations of consumption of specific food groups with disease status were identified. Participants with coronary heart disease, diabetes, hypertension, and cardiovascular disease were significantly more likely to report following a special diet and using low-calorie or low-sodium food products, however. Although the percentage of participants with prevalent disease who reported following special diets was relatively low from a clinical perspective, it was sufficiently high to suggest that controlling for dietary modifications may be important when attempting to identify associations of diet with prevalent disease in older populations.


Qualitative factors influencing breast and cervical cancer screening in women: A scoping review.
Breast and cervical are top cancers for women globally, but few studies have summarised how gender norms influence screening uptake, given sexual connotations and physical exposure. These beliefs may play a central role in decision-making, and understanding them is crucial to improving screening rates and services. This review scopes international literature for gender-based qualitative factors influencing women's screening uptake. A systematic search of peer-reviewed English articles in PubMed, Scopus, and CINAHL was conducted from inception until December 2019. Articles were included if they were about breast or cervical cancer screening, had mixed or qualitative methodology, and sampled women from the general population. 72 studies spanning 34 countries were analysed. Eight studies also included healthcare providers' views. Our narrative thematic analysis summarised primary themes extracted from each study into first-level subthemes, then synthesising second-level and third-level themes: (I) gender socialisation of women, (II) gender inequality in society, and (III) lack of empowerment to women in making screening decisions. Women tended to face sociocultural/role-based constraints, were expected to prioritise family, and keep bodily exposure to their husbands. Women showed low awareness and had fewer opportunities for health education compared to men. Male relations were often gatekeepers to financial resources needed to pay for screening tests. Screening risked community norms about women's or husbands' perceived embarrassing sexual behaviours. These findings suggest that interventions targeting unhelpful stigmatising beliefs about women's cancer screening must concurrently address community general norms, familial role-based beliefs, as well as at male relations who hold the purse-strings.


What do cytokine profiles tell us about subsets of juvenile idiopathic arthritis?
Classification of juvenile idiopathic arthritis is an ongoing process and up to now has been predominantly based on clinical manifestations--mainly number of joints at onset of disease. In the meantime, basic studies have advanced our knowledge regarding the disease pathogenesis. Unfortunately, studies of cytokines and cytokine polymorphisms have not followed the predominantly clinical International League of Associations for Rheumatology classification in that no significant biological differences among the different disease categories have been demonstrated with robust associations. Only systemic-onset disease seems to be quite different from other disease categories with regard to biologic mechanisms; indeed, it now seems closer to autoinflammatory than to classic autoimmune diseases. New players in the immunologic basis of juvenile idiopathic arthritis (eg, interleukin-17 and regulatory T cells) are also discussed in this review.


The effect of cold exposure on cerebral blood flow and cerebral available oxygen (aO2) in the rat and rabbit: thermoregulatory heat production by the brain and the possible role of neuroglia.
Simultaneous recordings of the effect of cold exposure on pulsatile cerebral impedance (PCI), heart rate (HR) and available oxygen (aO2) in the rat confirmed the conclusion, arrived at by recording (PCI + HR and aO2 separately, that the brain participates in thermoregulatory heat production. For statistical analysis of changes in cerebral metabolic rate (CMR) from experiments in which either only PCI + HR, or aO2 were recorded, changes in PCI and HR, i.e. in cerebral flood flow (CBF), and in a aO2 were combined into two indices (Index CMR/A and Index CMR/B) to indicate changes in CMR. Both indices demonstrated highly significant increases in CMR in response to cold in the rat and the young rabbit. In the rat, the magnitude of the response depended on stimulus intensity and on the distance from the surface of the brain, being greater near the surface than at greater depths. Circumstantial evidence suggests that the main source of thermoregulatory heat production in the brain has to be sought in the neuroglia.


Comparison of radiation dose and the effect of operator experience in femoral and radial arterial access for coronary procedures.
Radial access coronary procedures are associated with fewer access site complications compared to femoral access. There is controversy regarding greater radiation exposure to patient and operator using radial access. We aimed to compare radiation dose during coronary procedures for the 2 access routes and assess the effect of operator experience with radial access on radiation dose. Fluoroscopy time (FT) and dose-area product (DAP) were recorded for all radial access and femoral access procedures during default femoral access, transition phase (femoral access and early radial access), and default radial access. Femoral access cases (n = 848, 412 diagnostic, 436 percutaneous coronary interventions [PCIs]) and radial access cases (n = 965, 459 diagnostic, 506 PCIs) were assessed. For diagnostics, median FT for radial access was longer than for femoral access (4.43 minutes, interquartile range [IQR] 2.55 to 8.18, vs 2.34 minutes, IQR 1.49 to 4.18, p <0.001) and associated with larger DAP (radial access 1,837 μGy·m(2), IQR 1,172 to 2,783, vs femoral access 1,657 μGy·m(2), IQR 1,064 to 2,376, p <0.001). For PCI, FT was longer for radial access (median 12.02 minutes, IQR 7.57 to 17.54, vs femoral access 9.36 minutes, IQR 6.13 to 14.27, p <0.001)-this did not translate into an increased DAP (femoral access median 3,392 μGy·m(2), IQR 2,139 to 5,193, vs radial access 3,682 μGy·m(2), IQR 2,388 to 5,314, p = NS). For diagnostic radial access, FT decreased from the transition phase (n = 134) to the default radial access phase (n = 323, 5.12 minutes, IQR 3.07 to 9.40, vs 4.21 minutes, IQR 2.49 to 7.52, p = 0.03). This was not observed for PCI. In conclusion, transition from femoral access to radial access for diagnostics and PCI increased FT. DAP increased for diagnostic radial access but not PCI compared with femoral access. FTs for radial access diagnostic cases decreased with experience.


The four S's of wound management: staples, sutures, Steri-Strips, and sticky stuff.
Wound management is a daily occurrence in many practices. A short summary of current research in wound management is documented. Wound assessment guidelines are discussed. Included are evaluation of the patient's tetanus status, wound complexity and age, decisions as to the use of antibiotics, and closure methods. Follow-up care, patient education, and special considerations are also discussed. Billing information is considered. The objective of this article is that reader be able to: 1. Identify several closure options for commonly seen wounds 2. Identify selection criteria for use of Steri-Strips, sutures, and surgical glue in closing wounds and lacerations 3. Identify criteria indicating the need for antibiotics and the most common causative microbial agents associated with wounds 4. Identify over-the-counter (OTC) surgical glues and their popular uses 5. Evaluate immunization status and recommend appropriate treatment for wound prophylaxis.


Purification of long-chain acyl-CoA hydrolase from bovine heart microsomes and regulation of activity by lysophospholipids.
Long-chain acyl-CoA hydrolase (EC 188.8.131.52) has been purified 12,000-fold from bovine heart muscle microsomes by extraction with Miranol detergent, followed by column chromatography on Reactive Blue agarose and DEAE-cellulose. The purified enzyme was nearly homogeneous on polyacrylamide gel electrophoresis and had a molecular weight of 41,000 in the presence of dodecyl sulfate. The specificity and kinetic properties of the enzyme were studied using several acyl-CoA derivatives as potential substrates. The enzyme showed a wide degree of specificity with little dependence on either the fatty acyl chain length or the degree of unsaturation of the acyl group. The kinetic properties were in accord with the Michaelis-Menten equation under most conditions, although high concentrations of substrates generally inhibited the enzyme. Arachidonoyl-CoA, which was the most effective substrate, had a Km value of 0.4 microM and a Vmax value of 6.0 mumol min-1 mg-1. The enzyme was strongly and specifically inhibited by constants of 16 and 30 nM, respectively. Other lysolipids and detergents such as deoxycholate and Triton X-100 were weak inhibitors. These properties and others distinguish this enzyme from other acyl-CoA hydrolases and support the idea that lysophospholipids may be important in vivo in the regulation of lipid metabolism.