[Results of gastric bypass for morbid obesity after a follow up of seven to 10 years].
There is a paucity of information about the long term effects of gastric bypass for morbid obesity. To study the evolution of weight and complications of obesity, seven to 10 years after gastric bypass surgery. One hundred eighteen subjects with morbid obesity, aged 15 to 66 years (103 women), were followed for a mean of 94 months after surgery. Body weight, fasting blood glucose, total cholesterol, triglycerides and hemoglobin were measured before surgery and during follow up. At 24 months of follow up, all patients lost weight and there was a mild weight increase at 94 months, that paralleled the preoperative body mass index. Diabetes, hypercholesterolemia and hypertriglyceridemia subsided in 95, 87 and 94% of cases, respectively. Twenty percent of patients had mild anemia and 11% moderate or severe anemia. No patient recovered the preoperative weight. Weight reducing effects of gastric bypass are maintained after 94 months of follow up with the expected health benefits.


To validate hemoglobin (Hb) concentration in venous blood (VB) using the HemoCue 201+ in a subsample of children and women from the Mexican National Health and Nutrition Survey 2022. Prior to field work 50 HemoCue 201+ devices were verified using venous blood. During the field work 57 children (aged 1-11) and 62 women (aged 12-49) donated 3 mL of VB each. Hb was measured in each device of HemoCue 201+ and in a hematologic autoanalyzer for the validation. No significant bias was found in most of the devices. An adjustment criterion was used for 22 devices. Hb mean difference results were -0.049±0.578 g/dL in children and -0.098±0.628 g/dL in women. The HemoCue 201+ is a valid tool for estimating Hb concentration to produce reliable estimates of anemia prevalence when using venous blood.


Skin Cancer Concerns in People of Color: Risk Factors and Prevention
Background: Though people of color (POC) are less likely to become afflicted with skin cancer, they are much more likely to die from it due to delay in detection or presentation. Very often, skin cancer is diagnosed at a more advanced stage in POC, making treatment difficult.The purpose of this research was to improve awareness regarding skin cancers in people of color by providing recommendations to clinicians and the general public for early detection and photo protection preventive measures. Methods: Data on different types of skin cancers were presented to POC. Due to limited research, there are few resources providing insights for evaluating darkly pigmented lesions in POC. Diagnostic features for different types of skin cancers were recorded and various possible risk factors were considered. Results: This study provided directions for the prevention and early detection of skin cancer in POC based on a comprehensive review of available data. Conclusions: The increased morbidity and mortality rate associated with skin cancer in POC is due to lack of awareness, diagnosis at a more advanced stage and socioeconomic barriers hindering access to care. Raising public health concerns for skin cancer prevention strategies for all people, regardless of ethnic background and socioeconomic status, is the key to timely diagnosis and treatment.


Sphingolipids and glycerolipids. I. Chemical structures and ionophoretic activities of soya-cerebrosides I and II from soybean.
Two glycosphingolipids named soya-cerebrosides I and II were isolated from soybean, the seeds of Glycine max Merrill (Leguminosae), and their chemical structures have been elucidated on the basis of physicochemical evidence and several chemical degradation reactions. By using a newly constructed liquid membrane-type apparatus (W-08) for measurement of ion-transport and ion-binding activities and by employing a method using human erythrocyte membranes for measurement of ion-permeability, it has been found that soya-cerebroside II exhibits ionophoretic activity for Ca2+ ion.


Current practice of transradial approach for coronary procedures: A survey by the Italian Society of Interventional Cardiology (SICI-GISE) and the Italian Radial Club.
Transradial approach (TRA) for percutaneous coronary procedures is associated with improved patient outcome and is being increasingly adopted worldwide. We surveyed Italian interventional cardiologists in order to take a snapshot of the current practice of TRA. A web-based questionnaire was emailed to all members of the Italian Society of Interventional Cardiology. The survey was taken by 508 respondents. Cardiogenic shock and chronic total occlusions represented the principal limitations to TRA. Right TRA was the default approach for 81% of respondents. Both diagnostic and interventional procedures were routinely performed through 6 Fr sheaths (83% and 93%, respectively); dedicated TRA curves were used in 11% of diagnostic and in about 3% of interventional procedures. Almost 70% of the operators did not assess dual hand circulation. In case of crossover, the contralateral radial artery was the preferred site (57%). Radial artery hemostasis was mostly achieved by pneumatic bracelet (64%) and patency of the radial artery during hemostasis was ensured in 60% of cases. Pre-discharge patency of the radial artery was routinely assessed by almost 60% of respondents. For diagnostic procedures, adequate heparin anticoagulation (5000IU) was only given by 45% of operators. Most respondents believed that TRA is associated with greater radiation exposure for both the patient (82%) and the operator (98%) as compared to transfemoral approach. This survey provides contemporary data about the adoption of TRA in Italy and gives interesting insights about several technical and clinical issues related to the practice of this vascular approach for coronary procedures.


What is spared by fetal brain-sparing? Fetal circulatory redistribution and behavioral problems in the general population.
Intrauterine growth restriction has been linked to infant behavioral problems. While typically only birth weight is examined, here the authors assessed fetal circulatory redistribution, also called the "brain-sparing effect," which is a fetal adaptive reaction to placental insufficiency. They aimed to investigate whether fetal circulatory redistribution protects against behavioral problems. Within the Generation R Study (Rotterdam, the Netherlands, 2003-2007), fetal circulation variables for the umbilical artery and the middle and anterior cerebral arteries were assessed with Doppler ultrasound in late pregnancy. Ratios between placental resistance and cerebral resistance were related to behavioral problems, as measured by the Child Behavior Checklist, in 935 toddlers aged 18 months. The umbilical/anterior cerebral ratio was associated with the Total Problems summary score from the Child Behavior Checklist (per standard-deviation increase, odds ratio = 1.2, 95% confidence interval: 1.0, 1.5). Children with higher umbilical/anterior cerebral ratios had higher risks of internalizing problems, emotional reactivity, somatic complaints, and attention problems. A high umbilical/middle cerebral ratio was related to higher scores on the Internalizing and Somatic Complaints scales. The authors conclude that infants with circulatory redistribution in gestation are more likely to have behavioral problems. This suggests that "brain-sparing" does not completely spare the brain and indicates underlying pathology with consequences for later behavior.


A Systematic, Unbiased Mapping of CD8+ and CD4+ T Cell Epitopes in Yellow Fever Vaccinees.
Examining CD8+ and CD4+ T cell responses after primary Yellow Fever vaccination in a cohort of 210 volunteers, we have identified and tetramer-validated 92 CD8+ and 50 CD4+ T cell epitopes, many inducing strong and prevalent (i.e., immunodominant) T cell responses. Restricted by 40 and 14 HLA-class I and II allotypes, respectively, these responses have wide population coverage and might be of considerable academic, diagnostic and therapeutic interest. The broad coverage of epitopes and HLA overcame the otherwise confounding effects of HLA diversity and non-HLA background providing the first evidence of T cell immunodomination in humans. Also, double-staining of CD4+ T cells with tetramers representing the same HLA-binding core, albeit with different flanking regions, demonstrated an extensive diversification of the specificities of many CD4+ T cell responses. We suggest that this could reduce the risk of pathogen escape, and that multi-tetramer staining is required to reveal the true magnitude and diversity of CD4+ T cell responses. Our T cell epitope discovery approach uses a combination of (1) overlapping peptides representing the entire Yellow Fever virus proteome to search for peptides containing CD4+ and/or CD8+ T cell epitopes, (2) predictors of peptide-HLA binding to suggest epitopes and their restricting HLA allotypes, (3) generation of peptide-HLA tetramers to identify T cell epitopes, and (4) analysis of ex vivo T cell responses to validate the same. This approach is systematic, exhaustive, and can be done in any individual of any HLA haplotype. It is all-inclusive in the sense that it includes all protein antigens and peptide epitopes, and encompasses both CD4+ and CD8+ T cell epitopes. It is efficient and, importantly, reduces the false discovery rate. The unbiased nature of the T cell epitope discovery approach presented here should support the refinement of future peptide-HLA class I and II predictors and tetramer technologies, which eventually should cover all HLA class I and II isotypes. We believe that future investigations of emerging pathogens (e.g., SARS-CoV-2) should include population-wide T cell epitope discovery using blood samples from patients, convalescents and/or long-term survivors, who might all hold important information on T cell epitopes and responses.


Selective Labeling and Identification of the Tumor Cell Proteome of Pancreatic Cancer In Vivo.
Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest cancers. Dissecting the tumor cell proteome from that of the non-tumor cells in the PDAC tumor bulk is critical for tumorigenesis studies, biomarker discovery, and development of therapeutics. However, investigating the tumor cell proteome has proven evasive due to the tumor's extremely complex cellular composition. To circumvent this technical barrier, we have combined bioorthogonal noncanonical amino acid tagging (BONCAT) and data-independent acquisition mass spectrometry (DIA-MS) in an orthotopic PDAC model to specifically identify the tumor cell proteome in vivo. Utilizing the tumor cell-specific expression of a mutant tRNA synthetase transgene, this approach provides tumor cells with the exclusive ability to incorporate an azide-bearing methionine analogue into newly synthesized proteins. The azide-tagged tumor cell proteome is subsequently enriched and purified via a bioorthogonal reaction and then identified and quantified using DIA-MS. Applying this workflow to the orthotopic PDAC model, we have identified thousands of proteins expressed by the tumor cells. Furthermore, by comparing the tumor cell and tumor bulk proteomes, we showed that the approach can distinctly differentiate proteins produced by tumor cells from those of non-tumor cells within the tumor microenvironment. Our study, for the first time, reveals the tumor cell proteome of PDAC under physiological conditions, providing broad applications for tumorigenesis, therapeutics, and biomarker studies in various human cancers.


Leber's hereditary optic neuropathy: Update on the novel genes and therapeutic options.
A maternal inheritance disorder called Leber's hereditary optic neuropathy (LHON) is the most common primary mitochondrial DNA disorder. In most studies, there are more male patients than female patients, which contradicts the usual pattern in mitochondrial hereditary diseases. This suggests that nuclear DNA (nDNA) may influence the degeneration of retinal ganglion cells (RGCs) in LHON. The primary cause of this is dysfunction in complex I of the electron transport chain, leading to ineffective ATP production. In addition to MT-ND4 or MT-ND1 mutations, genes such as PRICKLE3, YARS2, and DNAJC30, which come from nuclear DNA, also play a role in LHON. These three genes affect the electron chain transport differently. PRICKLE3 interacts with ATP synthase (complex V) at Xp11.23, while YARS2 is a tyrosyl-tRNA synthetase 2 involved in mitochondria. DNAJC30 mutations result in autosomal recessive LHON (arLHON). Understanding how genes impact the disease is crucial for developing new treatments. Idebenone has been approved for treating LHON and has shown safety and efficacy in clinical trials. Mesenchymal stem cell-based therapy has also emerged as a potential treatment for LHON by transferring mitochondria into target cells. Gene therapy research focuses on specific gene mutations, and the wild-type ND4 gene target in the AAV vector has shown promise in clinical trials as a potential treatment for LHON.


Treatment of ruptured lenticulostriate artery aneurysms.
Lenticulostriate artery (LSA) aneurysms are rarely reported in the literature, making management decisions challenging. Conservative, endovascular, and surgical treatments have been described primarily through case reports and reports of individual authors' experiences. The purpose of this study is to report neurological outcomes in a single-institution experience of ruptured lenticulostriate aneurysms treated surgically. The authors have conducted a retrospective review of all cases involving patients with ruptured LSA aneurysms who presented to the Mt. Sinai Hospital neurosurgical service between September 2001 and January 2007. Over 5.4 years, the authors treated 6 patients with 7 LSA aneurysms-6 ruptured and 1 unruptured. The Hunt and Hess grade on admission ranged from I to IV, with subarachnoid hemorrhage in 5 of the 6 patients. Catheter angiography confirmed the presence of the aneurysms, and all patients underwent a pterional craniotomy and clipping or resection of the aneurysm, performed by a single surgeon. Associated risk factors in our series of patients included hypertension, cocaine abuse, and intracranial occlusive disease suggestive of moyamoya disease. Two types of LSA aneurysms were identified. The mean size of the 6 ruptured aneurysms was 3.2 mm. The LSA was preserved in 3 of 6 patients, but LSA preservation did not correlate with development of a postoperative infarct, clinically or radiologically. In patients with ruptured aneurysms, the mean modified Rankin Scale score at discharge was 1.7. The 3 patients in whom the LSA was sacrificed had good outcomes, suggesting that loss of the artery is clinically well tolerated. This case series demonstrates that surgical treatment of ruptured LSA aneurysms can be an appropriate, effective, and safe therapy.


Compartmental surgery in tongue tumours: description of a new surgical technique.
The aim of curative surgical oncology is to remove the primary tumour with a wide margin of normal tissue. What constitutes a sufficiently wide margin particularly in oral cancer is fundamentally unclear. The currently accepted standard is to remove the primary lesion with a 1.5-2 cm circumferential macroscopic margin. In the last ten years, anatomical considerations in the approach to primary, advanced and untreated tumours of the tongue led us to develop and improve a new surgical approach to their demolition and reconstruction. From July 1999 to July 2009, at the European Institute of Oncology in Milano, Italy, 155 patients were treated, while defining and refining the concept of compartmental tongue surgery (CTS) and its main components: 1) anatomical approach to the disease that requires removal of the primary lesion and all of the potential pathways of progression--muscular, lymphatic and vascular; 2) identification of a distinct territory at risk of metastatic representation of the disease: the parenchymal structures between the primary tumour and the cervical lymphatic chain that include the muscular (mylohyoid), neuro-vascular (lingual nerve and vein) and glandular (sublingual and submandibular) tissues; 3) preparation for a rational reconstruction in consideration of a functional defect resulting from this anatomical demolition.


Poly(I:C) causes failure of immunoprophylaxis to red blood cells expressing the KEL glycoprotein in mice.
Polyclonal anti-D (Rh immune globulin [RhIg]) therapy has mitigated hemolytic disease of the newborn over the past half century, although breakthrough anti-D alloimmunization still occurs in some treated females. We hypothesized that antiviral responses may impact the efficacy of immunoprophylaxis therapy in a type 1 interferon (IFN)-dependent manner and tested this hypothesis in a murine model of KEL alloimmunization. Polyclonal anti-KEL immunoprophylaxis (KELIg) was administered to wild-type or knockout mice in the presence or absence of polyinosinic-polycytidilic acid (poly[I:C]), followed by the transfusion of murine red blood cells (RBCs) expressing the human KEL glycoprotein. Anti-KEL alloimmunization, serum cytokines, and consumption of the transfused RBCs were evaluated longitudinally. In some experiments, recipients were treated with type 1 IFN (IFN-α/β). Recipient treatment with poly(I:C) led to breakthrough anti-KEL alloimmunization despite KELIg administration. Recipient CD4+ T cells were not required for immunoprophylaxis efficacy at baseline, and modulation of the KEL glycoprotein antigen occurred to the same extent in the presence or absence of recipient inflammation. Under conditions where breakthrough anti-KEL alloimmunization occurred, KEL RBC consumption by inflammatory monocytes and serum monocyte chemoattractant protein-1 and interleukin-6 were significantly increased. Poly(I:C) or type I IFN administration was sufficient to cause breakthrough alloimmunization, with poly(I:C) inducing alloimmunization even in the absence of recipient type I IFN receptors. A better understanding of how recipient antiviral responses lead to breakthrough alloimmunization despite immunoprophylaxis may have translational relevance to instances of RhIg failure that occur in humans.


Testing the Effectiveness of a Disclosure in Activating Children's Advertising Literacy in the Context of Embedded Advertising in Vlogs.
Watching vlogs of social media influencers has become a favorite pastime for children and adolescents. For advertisers, vlogs are an excellent way to reach young viewers. As such, vlogs have become a powerful marketing tool. However, for children and adolescents it is often unclear whether a vlog contains advertising, which raises questions regarding the fairness and transparency of this type of advertising. If children do not recognize the commercial intent of in-vlog advertising, then they are unlikely to activate their advertising literacy, which may serve as a critical coping mechanism. The aim of this study was to investigate if a sponsorship disclosure stimulates children and adolescents' (7-16 years old) to activate their advertising literacy when exposed to embedded advertising in vlogs and, subsequently, if advertising literacy activation is related to children's brand attitude. Furthermore, we investigated whether the relation between exposure to a sponsorship disclosure and advertising literacy activation was moderated by children's dispositional advertising literacy and their age. An innovative aspect of the current study is that advertising literacy activation was measured in two ways: with a self-reported questionnaire and via an indirect measurement task (Advertising Literacy Activation Task). The results showed that the children who were exposed to a sponsorship disclosure did not activate their advertising literacy to a higher extent than the children who were not exposed to such a disclosure. This might be because of the high prominence of the brand in the vlog; thus children may not have needed the disclosure to realize that the vlog was sponsored and accordingly activate their advertising literacy. The results also showed that stronger attitudinal advertising literacy activation led to a more negative brand attitude. Interestingly, this effect was only found when attitudinal advertising literacy was assessed with a questionnaire and not when it was assessed with the indirect measurement task. Thus, children who were more critical toward the in-vlog advertisement through self-reporting also had a more negative brand attitude. This suggests that direct and indirect measurements of advertising literacy activation reveal different processes through which children make sense of, and are affected by, advertising.


Intra-abdominal control of incidental indirect inguinal hernia.
A technique for dealing with incidental inguinal hernias during the course of other abdominal operations has been used on six patients in the past four years and kept the hernias reduced through the immediate postoperative period.


Proteomic and metabolomic responses of Pacific oyster Crassostrea gigas to elevated pCO2 exposure.
The gradually increased atmospheric CO2 partial pressure (pCO2) has thrown the carbonate chemistry off balance and resulted in decreased seawater pH in marine ecosystem, termed ocean acidification (OA). Anthropogenic OA is postulated to affect the physiology of many marine calcifying organisms. However, the susceptibility and metabolic pathways of change in most calcifying animals are still far from being well understood. In this work, the effects of exposure to elevated pCO2 were characterized in gills and hepatopancreas of Crassostrea gigas using integrated proteomic and metabolomic approaches. Metabolic responses indicated that high CO2 exposure mainly caused disturbances in energy metabolism and osmotic regulation marked by differentially altered ATP, glucose, glycogen, amino acids and organic osmolytes in oysters, and the depletions of ATP in gills and the accumulations of ATP, glucose and glycogen in hepatopancreas accounted for the difference in energy distribution between these two tissues. Proteomic responses suggested that OA could not only affect energy and primary metabolisms, stress responses and calcium homeostasis in both tissues, but also influence the nucleotide metabolism in gills and cytoskeleton structure in hepatopancreas. This study demonstrated that the combination of proteomics and metabolomics could provide an insightful view into the effects of OA on oyster C. gigas. The gradually increased atmospheric CO2 partial pressure (pCO2) has thrown the carbonate chemistry off balance and resulted in decreased seawater pH in marine ecosystem, termed ocean acidification (OA). Anthropogenic OA is postulated to affect the physiology of many marine calcifying organisms. However, the susceptibility and metabolic pathways of change in most calcifying animals are still far from being understood. To our knowledge, few studies have focused on the responses induced by pCO2 at both protein and metabolite levels. The pacific oyster C. gigas, widely distributed throughout most of the world's oceans, is a model organism for marine environmental science. In the present study, an integrated metabolomic and proteomic approach was used to elucidate the effects of ocean acidification on Pacific oyster C. gigas, hopefully shedding light on the physiological responses of marine mollusk to the OA stress.


All Yersinia Are Not Created Equal: Phenotypic Adaptation to Distinct Niches Within Mammalian Tissues.
Yersinia pseudotuberculosis replicates within mammalian tissues to form clustered bacterial replication centers, called microcolonies. A subset of bacterial cells within microcolonies interact directly with host immune cells, and other subsets of bacteria only interact with other bacteria. This establishes a system where subsets of Yersinia have distinct gene expression profiles, which are driven by their unique microenvironments and cellular interactions. When this leads to alterations in virulence gene expression, small subsets of bacteria can play a critical role in supporting the replication of the bacterial population, and can drive the overall disease outcome. Based on the pathology of infections with each of the three Yersinia species that are pathogenic to humans, it is likely that this specialization of bacterial subsets occurs during all Yersiniae infections. This review will describe the pathology that occurs during infection with each of the three human pathogenic Yersinia, in terms of the structure of bacterial replication centers and the specific immune cell subsets that bacteria interact with, and will also describe the outcome these interactions have or may have on bacterial gene expression.


Characteristics, Upon Presentation, of a Cohort of Patients with Vogt-Koyanagi-Harada Disease in Puerto Rico.
To describe the clinical features, upon initial presentation, of a cohort of patients with Vogt-Koyanagi-Harada (VKH) disease who live in Puerto Rico. A retrospective medical record review of patients with VKH was performed. The demographic and clinical characteristics were analyzed. Twenty-two patients who met the diagnostic criteria for VKH were identified and included in the analysis. The median age at presentation was 41 years; 68.2% were female, and all patients were Hispanics. Bilateral disease was present in 90.9% of patients, and 59.1% of patients were categorized as having probable VKH. A headache was reported in 54.5% of patients and was the most common complaint at the time of presentation; the second most common complaint was tinnitus, which was present in 22.7% of patients. Vitiligo, alopecia, and meningismus were each preset in 9.1% of patients while hearing loss and aseptic meningitis were each reported in 4.5% of patients. Seventy-seven percent of patients had either topical or systemic corticosteroid use prior to the initial encounter. Our study suggests that in Puerto Rico, patients with Vogt-Koyanagi-Harada disease may have a distinctive prevalence of characteristics at the presentation when compared to other ethnic groups, including other Hispanic cohorts.


[Chromosome aberrations in monocytic leukemias].
Improved cytogenetic techniques allow for the identification of subtle chromosomal rearrangements associated with particular subgroups of monocytic leukemias. A detailed assessment of both quantitative and structural chromosomal defects is presented and clinical and prognostic value of the karyotypic pattern is discussed.


Dietary patterns in Alzheimer's disease and cognitive aging.
Much of the attention on diet and Alzheimer's disease (AD) or cognition among the elderly has focused on the role of single nutrients or foods, while available information on dietary pattern (DP) analysis, which better reflects the complexity of the diet, is sparse. In this review, we describe different patterning approaches and present studies performed to date that have assessed the associations between DPs and risk of AD or cognitive function in the elderly. Three patterning approaches have been most commonly used: (i) hypothesis-based that use dietary quality indexes or scores (e.g. Mediterranean pattern), (ii) data-driven that use factor or cluster analysis to derive DPs, (iii) reduced rank regression which combines characteristics of the former two approaches. Despite differences existing among the approaches, DPs characterized by higher intake of fruits, vegetables, fish, nuts and legumes, and lower intake of meats, high fat dairy, and sweets seemed to be associated with lower odds of cognitive deficits or reduced risk of AD. Overall, the inherent advantages as well as the existing evidence of DP analyses strongly suggest that this approach may be valuable in AD and aging research. Further studies are warranted, though, to confirm the findings in different population settings, to address some methodological issues, and possibly utilize the information for future clinical trial design.


A randomized trial of traditional and golf-specific resistance training in amateur female golfers: Benefits beyond golf performance.
Compare golf-specific resistance training (GSRT) with traditional resistance training (TRAD) with regard to golf performance and other outcome measures. Randomized controlled study. Outpatient gym. 45 female golfers were randomized into TRAD or GSRT, both of which targeted muscles active during the golf swing. Participants performed supervised training 3d.wk-1 for 10 weeks. Golf performance, bone density, body composition, and physical performance tests. 29 individuals (58.1 ± 2.1y; 15 TRAD, 14 GSRT) completed training. Completers were older (p = 0.048) and played golf more frequently than non-completers (p = 0.002), but were not otherwise different. Training decreased whole body fat mass (p = 0.013) and visceral fat mass (p = 0.033) across groups, but did not influence lean mass (p = 0.283) or bone mineral density (p = 0.205). Training increased driver speed (p = 0.001), driver distance (p = 0.020), and 7I distance (p < 0.001), but not 7I speed (p = 0.160), but no group or interaction effects were present. Training increased all physical performance tests (p ≤ 0.005) regardless of group, but the seated medicine ball throw was most related to baseline driver speed (r2 = 0.384), and also most responsive to training (r2 = 0.250). 10 weeks of supervised TRAD and GSRT provided similar improvements in body composition, golf performance, and physical performance in amateur female golfers.


Genomic profile of metastatic breast cancer patient-derived xenografts established using percutaneous biopsy.
Metastatic breast cancer (mBC) is a complex and life-threatening disease and although it is difficult to cure, patients can benefit from sequential anticancer treatment, including endocrine therapy, targeted therapy and cytotoxic chemotherapy. The patient-derived xenograft (PDX) model is suggested as a practical tool to predict the clinical outcome of this disease as well as to screen novel drugs. This study aimed to establish PDX models in Korean patients and analyze their genomic profiles and utility for translational research. Percutaneous core needle biopsy or punch biopsy samples were used for xenotransplantation. Whole exome sequencing and transcriptome analysis were performed to assess the genomic and RNA expression profiles, respectively. Copy number variation and mutational burden were analyzed and compared with other metastatic breast cancer genomic results. Mutational signatures were also analyzed. The antitumor effect of an ATR inhibitor was tested in the relevant PDX model. Of the 151 cases studied, 40 (26%) PDX models were established. Notably, the take rate of all subtypes, including the hormone receptor-positive (HR +) subtype, exceeded 20%. The PDX model had genomic fidelity and copy number variation that represented the pattern of its donor sample. TP53, PIK3CA, ESR1, and GATA3 mutations were frequently found in our samples, with TP53 being the most frequently mutated, and the somatic mutations in these genes strengthened their frequency in the PDX model. The ESR1 mutation, CCND1 amplification, and the APOBEC signature were significant features in our HR + HER2- PDX model. Fulvestrant in combination with palbociclib showed a partial response to the relevant patient's tumor harboring the ESR1 mutation, and CCND1 amplification was found in the PDX model. AZD6738, an ATR inhibitor, delayed tumor growth in a relevant PDX model. Our PDX model was established using core needle biopsy samples from primary and metastatic tissues. Genomic profiles of the samples reflected their original tissue characteristics and could be used for the interpretation of clinical outcomes.


Dexamethasone effects on induction of neoplastic transformation by Fujinami sarcoma virus in an in vitro chick embryo periosteal model for osteosarcoma.
Recently we have developed a model in vitro system for the study of factors regulating the histogenesis of osteosarcoma. In this system, Fujinami sarcoma virus (FSV) induces osteosarcomatous changes such as increased cell proliferation and altered patterns of bone and nonmineralized matrix (osteoid) formation. Such changes can be quantitated at the individual cell level, by computer-assisted morphometry. Here we report on the effects of dexamethasone (DEX) on FSV-induced neoplastic transformation and osteogenesis in chick embryonic periosteum cultures, as reflected by a series of histopathological parameters. Most significantly, it was found that compared to 10(-9) M DEX treated cultures, in 10(-7) M DEX pretreated cultures, the bone/osteoid ratio was increased due to a relative increase in the area of bone and a decrease in the area of osteoid. The number of [3H]thymidine-labeled cells decreased significantly, while the proportion of alkaline phosphatase positive cells increased. Double-label immunohistochemistry (with anti-P140gag-fps) and histochemistry for alkaline phosphatase activity was performed, to demonstrate production of the oncogene-encoded protein, and osteoblastic differentiation, respectively. In an in vitro transformation assay single cells derived from 10(-9) M DEX treated cultures formed a significantly higher number of colonies than those obtained from 10(-7) M DEX pretreated cultures. Taken together, the data indicate that in the chick embryonic periosteum culture system, pretreatment with 10(-7) M DEX inhibits the ability of FSV to induce neoplastic transformation. This effect is probably the result of DEX-induced cell differentiation, prior to infection with FSV.


Acquisition of tomato yellow leaf curl virus by the whitefly Bemisia tabaci.
Tomato yellow leaf curl virus (TYLCV) genomic DNA can be detected by Southern blot analysis in nucleic acid extracted from a single whitefly. Acquisition of TYLCV by individual whiteflies in relation to the length of the access period, the virus concentration in, and the developmental stage of plant tissues was studied. The frequency of TYLCV detection increased with the length of the access-period; DNA was detected in 15% of whiteflies tested after a period of access to infected tissue of 30 min, regardless of whether it had a high or a low virus content (5 ng or 0.05 ng TYLCV DNA/micrograms plant chromosomal DNA), and in all insects tested after an 8 h period of access to all the plants. Those insects which had access to the youngest leaves of source plants, which have a high virus content, acquired detectable TYLCV DNA within 2 h. Insects which had access to a tissue for the same period acquired variable amounts of TYLCV DNA; insects feeding on plants with a low virus concentration acquired amounts of viral DNA comparable to those acquired by insects feeding on plants containing a 100-fold greater concentration of virus. Viruliferous insects retained TYLCV DNA for at least 13 days when placed on uninfected tomato plants. In these tests, whitefly could not acquire more than 600 million virus genomes (1 ng viral DNA), suggesting the existence of factors controlling the number of virions present in an insect.


Ampicillin vs. ampicillin-gentamicin prophylaxis in high-risk primary cesarean section.
A randomized, prospective comparison of ampicillin and ampicillin-gentamicin therapy was conducted in a group of 123 women undergoing primary cesarean section after the onset of labor. All pretreatment patient profiles indicated similar high-risk factors for infection. Febrile morbidity, complication rate and hospital stay were all more favorable in women receiving ampicillin-gentamicin.


An experimental strategy for quantitative analysis of the humoral immune response to prostate cancer antigens using natural protein microarrays.
The identification of human tumor antigens has potential utility in the diagnosis and treatment of cancers. We demonstrate here a complete strategy to profile immunoreactivity and identify tumor antigens from proteins derived from tumor cell lines. Microarrays of proteins produced from 2-D LC fractionation of prostate tumor cell-line lysates were used to profile immunoreactivity in the sera of prostate cancer patients and control subjects. Cancer-associated immunoreactivity to distinct groups of chromatography fractions was present in about 50% of the patients, with greater immunoreactivity present in patients with non-organ-confined cancer than in patients with organ-confined cancer. We grouped the immunoreactive fractions by similarities in elution order and patterns of immunoreactivity to guide and interpret the MS analysis of selected fractions, which was used to identify the proteins that may be responsible for the immunoreactivity. As a complementary method to further characterize and validate the immunoreactivity of the proteins identified by mass spectrometry, we demonstrate the use of focused microarrays of recombinant proteins. Disease-associated immunoreactivity was confirmed for one of the identified proteins, human Kallikrein 11. These results demonstrate a practical approach to screening, identifying, and validating immunoreactive proteins that could be applied to diverse studies on humoral immune responses.


Truth and consequences: a qualitative exploration of HIV disclosure in older adults.
While the number of older adults living with HIV/AIDS has increased substantially in recent years, research on HIV disclosure among this population is extremely limited. Studies on disclosure have typically not recruited older persons or have excluded age as a variable in the analysis. This study reports qualitative data from 25 in-depth interviews with older adults living with HIV disease. The ages ranged from 50-72 (mean 56.1; SD = 5.75). The interviews resulted in a model of disclosure patterns consisting of seven themes including protective silence, anticipatory disclosure, violations of confidentiality, unintentional disclosure and intentional disclosure. Approximately one quarter of informants had the confidentiality of their HIV status violated by others. Reasons for disclosure and non-disclosure given by older persons were similar to research among younger persons. Older individuals who intentionally disclosed their status to the broader society held generativity and the education of others (particularly younger adults) as important reasons for their actions.


Actinomyces marmotae sp. nov. and Actinomyces procaprae sp. nov. isolated from wild animals and reclassification of Actinomyces liubingyangii and Actinomyces tangfeifanii as Boudabousia liubingyangii comb. nov. and Boudabousia tangfeifanii comb. nov., respectively.
Four Gram-stain-positive, catalase-negative, non-spore-forming, rod-shaped bacterial strains (zg-325T, zg329, dk561T and dk752) were isolated from the respiratory tract of marmot (Marmota himalayana) and the faeces of Tibetan gazelle (Procapra picticaudata) from the Qinghai-Tibet Plateau of PR China. The results of 16S rRNA gene sequence-based phylogenetic analyses indicated that strains zg-325T and dk561T represent members of the genus Actinomyces, most similar to Actinomyces denticolens DSM 20671T and Actinomyces ruminicola B71T, respectively. The DNA G+C contents of strains zg-325T and dk561T were 71.6 and 69.3 mol%, respectively. The digital DNA-DNA hybridization values of strains zg-325T and dk561T with their most closely related species were below the 70 % threshold for species demarcation. The four strains grew best at 35 °C in air containing 5 % CO2 on brain heart infusion (BHI) agar with 5 % sheep blood. All four strains had C18:1ω9c and C16:0 as the major cellular fatty acids. MK-8 and MK-9 were the major menaquinones in zg-325T while MK-10 was predominant in dk561T. The major polar lipids included diphosphatidylglycerol and phosphatidylinositol. On the basis of several lines of evidence from phenotypic and phylogenetic analyses, zg-325T and dk561T represent novel species of the genus Actinomyces, for which the name Actinomyces marmotae sp. nov. and Actinomyces procaprae sp. nov. are proposed. The type strains are zg-325T (=GDMCC 1.1724T=JCM 34091T) and dk561T (=CGMCC 4.7566T=JCM 33484T). We also propose, on the basis of the phylogenetic results herein, the reclassification of Actinomyces liubingyangii and Actinomyces tangfeifanii as Boudabousia liubingyangii comb. nov. and Boudabousia tangfeifanii comb. nov., respectively.


Central DXA utilization shifts from office-based to hospital-based settings among medicare beneficiaries in the wake of reimbursement changes.
In the United States, Medicare gradually reduced payments for central dual-energy X-ray absorptiometry (DXA) performed at physician offices (or other nonhospital settings) from an average of $139 in 2006 to about $82 in 2007 and 2008 and $72 in 2009. Reimbursement for hospital outpatient DXA service was unchanged. We investigated the utilization of hip and spine (central) DXA in the Medicare population before and after the reduction. We identified individuals from the national 5% random sample of Medicare beneficiaries who were ≥65 years of age and enrolled in Medicare Parts A and B but not in a Medicare Advantage plan from 2002 through 2009. For each calendar year, we calculated the proportion of beneficiaries who submitted claims for DXA, the proportions of DXAs performed in hospitals and in physician offices and the number of physician office-based practices that discontinued or started to provide DXA services. From 2002 to 2006, the proportion of beneficiaries who had at least one central DXA increased from 7.9% to 9.6% at an annual increase of 0.4% and from 2006 to 2009, the annual increase dropped to 0.1%. The number of DXAs performed in physician offices dropped from 1,643,720 (69% of 2,363,500 total DXAs) in 2006 to 1,534,240 (66% of 2,338,240) in 2009. This decline was offset by an increase in the number of DXAs performed in hospitals, which increased from 719,780 (31%) in 2006 to 804,000 (34%) in 2009. Among physician office-based practices, more practices initiated than discontinued DXA service each year from 2002 to 2006. However, the trend was reversed since 2007 such that in 2009, 1876 practices discontinued and only 1394 initiated DXA service. The reduction in DXA reimbursement was associated with a decrease in the number of DXAs performed in physician offices and fewer physician offices that provided DXA services.


Regional adipose tissue and elevations in serum aminotransferases in HIV-infected individuals.
The association of fat distribution with alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevations is not well-defined in HIV-infected individuals. Obesity is associated with hepatic steatosis, and ALT is a marker of steatosis in the general population. Cross-sectional analysis of 1119 HIV-infected and 284 control subjects. Hepatitis C virus (HCV) RNA testing determined HCV infection. Magnetic resonance imaging measured regional adipose tissue volume. After adjustment for demographic and lifestyle factors, visceral adipose tissue (VAT) was positively associated with ALT in HIV/HCV-coinfected subjects (+9.8%, 95% confidence interval [CI]: 2.8 to 17.6), HIV-monoinfected subjects (+8.0%, 95% CI: 4.2 to 12.1), and controls (+5.9%, 95% CI: 2.0 to 10.1). In contrast, lower trunk subcutaneous adipose tissue (SAT) was negatively associated with ALT in HIV/HCV-coinfected subjects (-14.3%, 95% CI: -24.7 to -4.2) and HIV-monoinfected subjects (-11.9%, 95% CI: -18.4 to -5.3); there was a trend toward an association in controls (-7.1%, 95% CI: -22.7 to 5.9). Estimated associations between regional adipose tissue and AST were small and did not reach statistical significance. More VAT and less lower trunk SAT are associated with elevated ALT, which likely reflects the presence of steatosis. There was little association with AST. HCV infection and having more VAT or less lower trunk SAT are independently associated with elevated ALT in HIV infection. Study regarding the association between VAT, trunk SAT, HCV, and progression of steatosis and fibrosis is needed in HIV-infected individuals.


Magnetically-responsive self assembled composites.
This tutorial review summarizes the recent advances on the self assembly of magnetic nanoparticles into one-, two-, and three-dimensional architectures using synthetic polymers and biopolymers. The materials have unique stimuli-responsive behavior that emerge in response to internal and external magnetic fields. For example, magnetic fields can be used to elicit a magnetic response from the materials, whether the material rearranges in response to the external field, or provides information regarding the local environment of the nanoparticles. These materials hold great promise for applications ranging from data storage to nanomedicine.


Exudative lung injury is associated with decreased levels of surfactant proteins in a rat model of meconium aspiration.
Meconium aspiration syndrome remains a common cause of respiratory failure in neonates. The acute effects of meconium aspiration are inactivation of lung surfactant in vivo and in vitro. This study investigated the delayed effects of meconium on alveolar surfactant phospholipids and protein levels in spontaneously breathing animals. Twenty-two adult rats were given 4.3 mg of dry weight human meconium after endotracheal intubation. Rats were briefly mechanically ventilated in room air, extubated, then killed after 16 (n = 6), 24 (n = 6), 48 (n = 6), and 72 hours (n = 4). Control animals received the same volume of normal saline (n = 7) or no meconium (n = 7). Bronchoalveolar lavage and tissue specimens were evaluated for inflammatory cells, total proteins, surfactant phospholipids, and surfactant proteins. Meconium caused exudative lung injury that was reflected in increased cell counts and proteins in alveolar lavage fluid. The peak injury occurred at 16 hours after instillation, whereas recovery occurred by 72 hours. Although total lavage fluid phospholipids did not change over time, phospholipid and dipalmitoyl phosphatidylcholine in large aggregates tended to decrease at 24 hours. Western blot analysis demonstrated time-dependent qualitative decreases in surfactant proteins A and B (SP-A, SP-B) in meconium-instilled animals compared with the controls. ELISA for SP-B confirmed the Western blot findings with total SP-B in large aggregate decreasing from 25 +/- 4 microg in controls to 6.6 +/- 0.8 microg at 24 hours of injury. Our study suggests that the exudative lung injury with meconium instillation is associated with decreased levels of SP-A and SP-B in the large aggregate fraction of lung surfactant. We speculate that decreased secretion and/or increased degradation accounts for lower levels of SP-B in bronchoalveolar lavage fluid.


Radiation therapy for recurrent heterotopic ossification prophylaxis after partial metatarsal amputation.
The formation of heterotopic ossification is a relatively common, yet rarely discussed, cause of re-ulceration after previous partial metatarsal amputation. Excessive bone growth at the amputation site has the potential to create an unwanted prominence on the weightbearing surface of the foot, intuitively increasing plantar pressure and placing the neuropathic patient at greater risk of re-ulceration and limb loss. The aim of the present study was to assess the efficacy of single-dose radiation therapy in preventing recurrent heterotopic ossification. The inclusion criteria consisted of a history of clinically relevant heterotopic ossification formation after partial metatarsal amputation with subsequent partial metatarsal amputation for heterotopic ossification resection, followed by prophylactic single-dose radiation therapy. Eleven consecutive patients meeting the inclusion criteria were identified for the present study. Before the intervention, 10 (91%) patients demonstrated formation of mid- to high-grade heterotopic ossification, and 9 (82%) patients exhibited an associated neuropathic ulceration. On follow-up at least 6 weeks after intervention, 2 (18%) patients exhibited low-grade heterotopic ossification reformation that was not clinically relevant and 9 (82%) did not show signs of heterotopic recurrence. Single-dose radiation therapy can help prevent the formation of heterotopic ossification in high-risk patients, acting as an effective adjunct to surgery in minimizing the risk of re-ulceration and re-amputation in the neuropathic patient.


First trimester HtrA1 maternal plasma level and spontaneous preterm birth.
High temperature requirement A1 (HtrA1) is a serine protease detected in maternal plasma and in placental tissues during normal gestation and in various pathological conditions. The purpose of this study was to determine whether the maternal plasma concentration of HtrA1 in first trimester, alone or combined with other maternal factors, can be used to identify women at risk for spontaneous preterm birth (SPTB). This is a cohort study on pregnant women at 12 weeks of gestation recruited between 2014 and 2016 and prospectively followed until delivery. One hundred and fifty-nine women were included in the study: 140 women delivered at term and 19 (11.9%) delivered spontaneously preterm. Plasma samples were assessed for HtrA1 by ELISA and data were compared between women which delivered at term with women which delivered preterm. A multiple logistic regression analysis was used to estimate the independent effect of women's characteristics on the probability of a SPTB. SPTB was significantly associated with log HtrA1 values at 12 weeks of gestation, BMI before pregnancy and physical activity. In particular, the probability of a SPTB increases of 79% for every added unit of log HtrA1, while decreases of 18% for every added unit of BMI. In addition, physical activity was found as an important protective factor. The ROC curve showed that the model had a good accuracy in predicting SPTB, with an AUC equal to 0.83 (95%CI: 0.73-0.91). Maternal plasma HtrA1 may be considered a marker of SPTB. In addition, our model indicates two factors that could be modified to reduce the risk of SPTB, i.e. BMI before pregnancy and maternal physical activity.


Highly resistant gram-negative microorganisms: incidence density and occurrence of nosocomial transmission (TRIANGLe Study).
The objectives of this study were to determine the incidence density and the occurrence of horizontal spread of highly resistant gram-negative rods (HR-GNRs) in Dutch hospitals. The factors that influence these outcome measures were also investigated. All patients with HR-GNRs, as determined by sample testing, who were hospitalized in 1 of 18 hospitals during a 6-month period (April through October 2007) were included in this study. For all available isolates, the species was identified, susceptibility was determined (including the presence of extended-spectrum β-lactamases [ESBLs]), and molecular typing was performed. On the basis of a combination of species identification, molecular typing, and epidemiological data, the occurrence of nosocomial transmission was determined. The mean incidence density of patients with HR-GNRs was 55 per 100,000 patient-days (cumulative incidence, 39 per 10,000 patients admitted). A facility being a university hospital was a statistically significant (P = .03) independent determinant of a higher incidence of patients with HR-GNRs. The majority of HR-GNR isolates were ESBL producers. The adjusted transmission index-the ratio between secondary and primary cases-in the participating hospitals ranged from 0.0 to 0.2. The overall adjusted transmission index of HR-GNRs was 0.07. No determinants for a higher transmission index were identified. The nosocomial transmission rate of HR-GNRs was relatively low in all hospitals where well-established transmission-based precautions were used. The incidence density of patients with HR-GNRs was higher in university hospitals, probably due to the patient population and the complexity of the care provided.


Neurodynamic response analysis of anterior semicircular canal afferents in the pigeon.
1. The neurodynamic responses to sinusoidal and pulse angular accelerations were studied in anterior semicircular canal afferents in the barbiturate-anesthetized pigeon. 2. The resting discharge frequency, aS, varied from 7.4 to 149.0 impulses/s. For most units, aS remained fairly constant for long periods of time during the experiment. 3. The neural-response harmonic distortion, resulting from stimulation by sinusoidal angular accelerations, varied in different units. Percent distortions from as low as 3% to those as high as 57% were determined. 4. Intensity-function plots of peak first harmonic neural response as a function of the peak sinusoidal angular acceleration (with frequency, f, as a parameter) are of two types: one has a linear relationship between the variables; the other demonstrates pronounced nonlinearities ("saturation," particularly for low values of f). In saturation-type units, the data of which fit a power law function, the exponent of the function is frequency dependent, becoming closer and closer to unity with increasing f. 5. Data for all units fit the transfer function, G'(s) = Csk/(tauLS + 1), where G'(s) relates the unit response to angular acceleration, C is a gain constant, 0 < k < 1, and tauL is the so-called long time constant of the classical torsion pendulum model. tauL varied from 4.45 to 22.17 S (mean +/- SE = 10.24 +/- 1.20 S). This may be interpreted as an indication of a regional distribution of tauL'S within the neuroepithelium. Arguments are advanced to show that this is consistent with our present understanding of the ampullary end organ. 6. The degree of regularity of the spontaneous discharge (as determined by the coefficient of variation, CV) was significantly correlated with the parameter k in G'(S). The larger the CV, the larger is the corresponding k. Further work indicated that the larger the value of k, the more adaptation a unit exhibited (k varied from 0.017 to 0.66). 7. The time-domain response of G(S) = G'(S)/(tauSS + 1) to different durations of pulse angular acceleration stimuli agreed well with the neural response to these stimuli (tauS = 2.27 ms is the short time constant of the torsion pendulum model). 8. The term Sk was decomposed into an expression containing a series of polynomials in S in the numerator and denominator. The first term in this expansion K0tau1S/(tau1S + 1), has previously been shown to describe so-called adaptation properties in the dynamics of the semicircular canals. A mean (+/-SE) tau1 = 71.56 (+/-10.01) S was determined. Evidence is presented that Sk probably represents a relaxation phenomenon comprised of a time-varying intracellular Na+/K+-transport process, components of which are summed with the generator potential in the afferent terminal(S) of the receptor hair cell.


Derivation and validation of a risk-factor model for detection of oral potentially malignant disorders in populations with high prevalence.
Oral and pharyngeal cancers constitute the sixth most common type of cancer globally, with high morbidity and mortality. In many countries, most cases of oral cancer arise from long-standing, pre-existing lesions, yet advanced malignancies prevail. A new approach to early detection is needed. We aimed to validate a model for screening so that only high-risk individuals receive the clinical examination. A community-based case-control study (n=1029) in rural Sri Lanka assessed risk factors and markers for oral potentially malignant disorders (OPMD) by administering a questionnaire followed by an oral examination. We then developed a model based on age, socioeconomic status and habits of betel-quid chewing, alcohol drinking and tobacco smoking, with weightings based on odds ratios from the multiple logistic regression. A total, single score was calculated per individual. Standard receiver-operator characteristic curves were plotted for the total score and presence of OPMD. The model was validated on a new sample of 410 subjects in a different community. A score of 12.0 produced optimal sensitivity (95.5%), specificity (75.9%), false-positive rate (24.0%), false-negative rate (4.5%), positive predictive value (35.9%) and negative predictive value (99.2%). This model is suitable for detection of OPMD and oral cancer in high-risk communities, for example, in Asia, the Pacific and the global diaspora therefrom. A combined risk-factor score of 12.0 was optimal for participation in oral cancer/OPMD screening in Sri Lanka. The model, or local adaptations, should have wide applicability.


Fish Intake May Affect Brain Structure and Improve Cognitive Ability in Healthy People.
As the population ages worldwide, the prevalence of cognitive disorders including mild cognitive impairment (MCI) is increasing. MCI appears in 10-20% of adults aged 65 years and older and is generally referred to as an intermediate stage between normal cognitive aging and dementia. To develop timely prevention and early treatment strategies by identifying biological factors, we investigated the relationship between dietary consumption of fish, brain structure, and MCI in cognitively normal subjects. The brain structure was assessed using neuroimaging-derived measures including the "gray-matter brain healthcare quotient (GM-BHQ)" and "fractional-anisotropy brain healthcare quotient (FA-BHQ)," which are approved as the international standard (H.861.1) by the International Telecommunication Union Telecommunication Standardization Sector. Dietary consumption of fish was calculated using the brief self-administered diet history questionnaire (BDHQ), and MCI was assessed using the Memory Performance Index (MPI) of MCI screening method (MCI Screen). This study showed that fish intake was positively associated with both FA-BHQ and MPI, and FA-BHQ was more strongly associated with MPI than fish intake. Our findings are in line with those in previous studies, but our study further indicates that the condition of the whole brain integrity measured by the FA-BHQ may mediate the relationship between fish intake and MCI prevention in healthy people. In other words, FA-BHQ may be used to identify people at high risk of MCI to provide the appropriate intervention.


Exploration of interactions between prognostic factors of stage I malignant melanoma.
While many studies have sought prognostic factors of malignant melanoma using multivariate survival models, the interaction between predictors has been much less studied. We have studied data from 1,560 patients with stage I melanoma collected at the Cancer Registry of the Canton of Zurich over the period 1980-1990 and explored interactions between predictors by identifying two separate multivariate Cox models for men and women and investigating two-way interactions between predictors in each model. Considerable differences between models for man and women were observed. In particular, in women a pronounced interaction between 'histology' and 'Clark level' was identified. Without this interaction 'histology' and 'Clark level' are not significant but when the interaction term was included both predictors become significant. Thus, omission of an interaction term may preclude the recognition of main effects ('masking'). For female patients with nodular tumours prognosis is essentially independent of Clark level. In contrast, for female patients with non-nodular tumours, prognosis was found to be strongly dependent on Clark level. In the case of Clark level 2 prognosis was extremely good: no patient was observed to die from melanoma. We conclude that it may be worth considering interaction terms. With large enough sample sizes it may be preferable to stratify patients into subgroups and to identify separate models for each stratum instead of having to cope with interactions of higher order.


Aligning health care policy with evidence-based medicine: the case for funding direct oral anticoagulants in atrial fibrillation.
Misalignment between evidence-informed clinical care guideline recommendations and reimbursement policy has created care gaps that lead to suboptimal outcomes for patients denied access to guideline-based therapies. The purpose of this article is to make the case for addressing this growing access barrier to optimal care. Stroke prevention in atrial fibrillation (AF) is discussed as an example. Stroke is an extremely costly disease, imposing a significant human, societal, and economic burden. Stroke in the setting of AF carries an 80% probability of death or disability. Although two-thirds of these strokes are preventable with appropriate anticoagulation, this has historically been underprescribed and poorly managed. National and international guidelines endorse the direct oral anticoagulants as first-line therapy for this indication. However, no Canadian province has provided these agents with an unrestricted listing. These decisions appear to be founded on silo-based cost assessment-the drug costs rather than the total system costs-and thus overlook several important cost-drivers in stroke. The discordance between best scientific evidence and public policy requires health care providers to use a potentially suboptimal therapy in contravention of guideline recommendations. It represents a significant obstacle for knowledge translation efforts that aim to increase the appropriate anticoagulation of Canadians with AF. As health care professionals, we have a responsibility to our patients to engage with policy-makers in addressing and resolving this barrier to optimal patient care.


Adherence to EAT-Lancet dietary recommendations for health and sustainability in the Gambia.
Facilitating dietary change is pivotal to improving population health, increasing food system resilience, and minimizing adverse impacts on the environment, but assessment of the current 'status-quo' and identification of bottlenecks for improvement has been lacking to date. We assessed deviation of the Gambian diet from the EAT-Lancet guidelines for healthy and sustainable diets and identified leverage points to improve nutritional and planetary health. We analysed the 2015/16 Gambian Integrated Household Survey dataset comprising food consumption data from 12 713 households. Consumption of different food groups was compared against the EAT-Lancet reference diet targets to assess deviation from the guidelines. We computed a 'sustainable and healthy diet index (SHDI)' based on deviation of different food groups from the EAT-Lancet recommendations and modelled the socio-economic and geographic determinants of households that achieved higher scores on this index, using multivariable mixed effects regression. The average Gambian diet had very low adherence to EAT-Lancet recommendations. The diet was dominated by refined grains and added sugars which exceeded the recommendations. SHDI scores for nutritionally important food groups such as fruits, vegetables, nuts, dairy, poultry, and beef and lamb were low. Household characteristics associated with higher SHDI scores included: being a female-headed household, having a relatively small household size, having a schooled head of the household, having a high wealth index, and residing in an urban settlement. Furthermore, diets reported in the dry season and households with high crop production diversity showed increased adherence to the targets. While average Gambian diets include lower amounts of food groups with harmful environmental footprint, they are also inadequate in healthy food groups and are high in sugar. There are opportunities to improve diets without increasing their environmental footprint by focusing on the substitution of refined grains by wholegrains, reducing sugar and increasing fruit and vegetables consumption.


A framework for modeling epistatic interaction.
Recently, various tools for detecting single nucleotide polymorphisms (SNPs) involved in epistasis have been developed. However, no studies evaluate the employed statistical epistasis models such as the χ2-test or quadratic regression independently of the tools that use them. Such an independent evaluation is crucial for developing improved epistasis detection tools, for it allows to decide if a tool's performance should be attributed to the epistasis model or to the optimization strategy run on top of it. We present a protocol for evaluating epistasis models independently of the tools they are used in and generalize existing models designed for dichotomous phenotypes to the categorical and quantitative case. In addition, we propose a new model which scores candidate SNP sets by computing maximum likelihood distributions for the observed phenotypes in the cells of their penetrance tables. Extensive experiments show that the proposed maximum likelihood model outperforms three widely used epistasis models in most cases. The experiments also provide valuable insights into the properties of existing models, for instance, that quadratic regression perform particularly well on instances with quantitative phenotypes. The evaluation protocol and all compared models are implemented in C++ and are supported under Linux and macOS. They are available at https://github.com/baumbachlab/genepiseeker/, along with test datasets and scripts to reproduce the experiments. Supplementary data are available at Bioinformatics online.


Leisure boredom and adolescent risk behaviour: a systematic literature review.
There has been very little research investigating leisure boredom and risk behaviour among adolescents in South Africa. A systematic review of literature was conducted to synthesise current knowledge within the field of leisure boredom and risk behaviour among adolescents. An online and a hand search for relevant articles were conducted using keywords. This resulted in the retrieval of 25 articles that met the inclusion criteria. It was evident that the experience of leisure boredom is influenced by a variety of different factors, not least of which is the environment or context within which adolescents are situated. A key finding was how few studies have focussed on leisure boredom and risk behaviour in adolescents, particularly in the developing world. Also, gaps in the knowledge basis were identified, thus providing direction for future research. The review focuses attention on leisure boredom as a factor contributing to risk behaviour in adolescents. Expanding knowledge in this area is useful for individuals and organisations concerned with adolescent health, education and development.


Characterization of major recognition sequences for a herpes simplex virus type 1 origin-binding protein.
To investigate early initiation events in the replication of herpes simplex virus type 1, we analyzed interactions of proteins from infected cell extracts with the small origin of herpes simplex virus type 1 (oris1). Using the mobility shift assay, we detected two origin-specific binding interactions. We characterized the more prominent interaction on both strands of the DNA duplex with DNase I protection and methylation interference assays. Protein binding protects 17 bases of DNA on each strand from DNase I. These sequences are located at the left end of the central palindrome and are shifted four bases relative to one another. On the basis of the DNase protection pattern, we believe this protein to be related to the origin-binding protein defined by Elias et al. (P. Elias, M.E. O'Donnell, E.S. Mocarski, and I.R. Lehman, Proc. Natl. Acad. Sci. 83:6322-6326, 1986). Our DNase I footprint shows both strong and weak areas of protection. The regions strongly protected from DNase I align with the essential contact residues identified by interference footprinting. Methylation interference defines a small binding domain of 8 base pairs: 5'-GTTCGCAC-3'/3'-CAAGCGTG-5'. This recognition sequence contains two inverted 5'-GT(T/G)CG-3' repeats which share a 2-base overlap; thus, the origin-binding protein probably binds to the inverted repeats as a dimer.


All-cause, cardiovascular, and cancer mortality in western Alaska Native people: western Alaska Tribal Collaborative for Health (WATCH).
We determined all-cause, cardiovascular disease (CVD), and cancer mortality in western Alaska Native people and examined agreement between death certificate information and adjudicated cause of deaths. Data from 4 cohort studies were consolidated. Death certificates and medical records were reviewed and adjudicated according to standard criteria. We compared adjudicated CVD and cancer deaths with death certificates by calculating sensitivity, specificity, predictive values, and κ statistics. Men (n = 2116) and women (n = 2453), aged 18 to 95 years, were followed an average of 6.7 years. The major cause of death in men was trauma (25%), followed by CVD (19%) and cancer (13%). The major cause of death in women was CVD (24%), followed by cancer (19%) and trauma (8%). Stroke rates in both genders were higher than those of US Whites. Only 56% of deaths classified as CVD by death certificate were classified as CVD by standard criteria; discordance was higher among men (55%) than women (32%; κs = 0.4 and 0.7). We found lower rates for coronary heart disease death but high rates of stroke mortality. Death certificates overestimated CVD mortality; concordance between the 2 methods is better for cancer mortality. The results point to the importance of cohort studies in this population in providing data to assist in health care planning.


Multi-layered PZT/polymer composites to increase signal-to-noise ratio and resolution for medical ultrasound transducers.
Increasing transducer bandwidth and signal-to-noise ratio (SNR) is fundamental to improving the quality of medical ultrasound images. In previous work, the authors have proposed the use of multi-layer 1-3 PZT/epoxy composites to increase both but have encountered significant fabrication challenges. These difficulties include making the bond thickness between the layers extremely small relative to the ultrasound wavelength and aligning the posts of the composite to increase the coupling coefficient. The authors have routinely achieved a bond thickness of less than 5 mum but aligning the posts is more complicated. Finite element (PZFlex; Weidlinger, Assoc., New York, NY and Los Altos, CA) simulations show that the pulse-echo SNR and bandwidth degrade significantly with misalignment of the posts. Alignment of greater than 90% of the post pitch (i.e., tolerance of 10 to 20 mum) is required to obtain significant increases in SNR and bandwidth relative to conventional transducer arrays. This will be a difficult tolerance for large-scale production. Thus, the authors have developed a multi-layer composite hybrid array that will not require post alignment. This structure consists of a layer of 5 MHz 1-3 composite material on top of conventional 5 MHz PZT, which will provide greater SNR relative to conventional composites and increased bandwidth over multi-layer PZT. PZFlex simulations show that for a 2 MHz linear array element, the 2 layer hybrid structure increases the pulse-echo SNR by 7.5 dB over that from a single layer PZT element. Even without a matching layer, an increase in the -6 dB pulse-echo fractional bandwidth from 22% for the PZT element to 35% for the hybrid element was also predicted. Experimentally, in a 32 element array, the authors achieved an increase of 5.2 dB in SNR and an increased -6 dB bandwidth from 23 to 30%. In vitro and in vivo images showed corresponding improvements.


Comparative analysis of the genes encoding 23S-5S rRNA intergenic spacer regions of Lactobacillus casei-related strains.
In this study, investigations into the 23S-5S rRNA intergenic spacer regions (ISRs) of the Lactobacillus casei group were performed. A 1.6 kb fragment, from Lactobacillus paracasei strain ATCC 27092, containing part of the 5S rRNA gene (60 bp), the 5S-23S spacer region (198 bp) and part of the 23S rRNA gene (1295 bp) was cloned and sequenced (GenBank no. AF098107). This fragment was used as a probe to determine the rRNA restriction fragment length polymorphism (RFLP) patterns of nine strains belonging to the Lactobacillus casei group, along with four other non-Lactobacillus casei lactobacilli species. A pair of PCR primers, 23-Fl and 5-Ru, was designed and used for PCR amplification of the 23S-5S rRNA ISRs of these strains. The ISR length and sequence polymorphisms provided additional information for the taxonomic study of the Lactobacillus casei group. The spacer-length polymorphism of Lactobacillus rhamnosus was distinct from those of the other strains and this observation is consistent with the classification of Lactobacillus rhamnosus proposed by Mori et al. For all Lactobacillus casei and Lactobacillus paracasei strains, two major bands (approx. 250 and 170 bp in size) were obtained except in the case of Lactobacillus paracasei subsp. tolerans strain NCIMB 9709T, which yielded only one amplified product (250 bp). The sequencing data of the PCR products of seven well-characterized Lactobacillus casei and Lactobacillus paracasei strains revealed the presence of a 76/80 bp insertion/deletion with some random, single-base substitutions between the longer and shorter spacers for each respective strain. A few base variations were also detected within different strains in this group although the overall sequence similarity was very high (95.9-99.5%). The rRNA RFLP and the spacer sequence of Lactobacillus casei type strain ATCC 393T exhibited unique identities in this cluster. On the other hand, Lactobacillus casei strain ATCC 334 showed a high level of similarity with the other Lactobacillus casei strains tested. These observations lend some support to the request for the reassignment of strain ATCC 334 as the neotype of Lactobacillus casei subsp. casei in place of strain ATCC 393T.


Bone steady-state is established at reduced bone strength after spinal cord injury: a longitudinal study using peripheral quantitative computed tomography (pQCT).
Spinal cord injury (SCI) is associated with a marked and rapid sublesional bone loss. So far, reports about the time course of adaptive changes in bone mass and structure in people with chronic and complete SCI are conflicting. Both, a continuous decline of bone parameters throughout the chronic phase of immobilisation as well as stabilisation of bone status on a low level have been documented. In our recently published cross-sectional study we suggested that subjects with a complete SCI reach a new bone steady-state in the paralysed limbs after extensive bone loss was complete. In addition, we described a time loss curve for each measured bone mineral density and geometry parameter and calculated its individual time to reach steady-state (tsteady-state). The aim of the present study was to test the findings of our cross-sectional study in a longitudinal design. Thirty-nine male subjects of the original cross-sectional study with complete SCI and paralysis duration between 0.9 and 34 years were included. Two follow-up pQCT measurements at 15 and 30 months after baseline measurement were performed at the distal epiphyses and mid shafts of the femur, tibia and radius. From the epiphyseal scans, bone mass, trabecular and total BMD were calculated. From the shaft scans, bone mass and cortical BMD, total and cortical cross-sectional areas and cortical thickness were determined. Repeated measures ANOVAs were performed with bone data at baseline, after 15 months and 30 months. Analyses were performed including only subjects with a lesion duration > or =t(steady-state) for each particular bone parameter. Bone parameters of tibial and femoral epi- and diaphyses were found to show no statistically significant differences between the three time points. Relative changes in bone parameters were small and ranged from -1.72% to +0.51% in the femur and from -1.67% to +0.42% in the tibia within 30 months of monitoring. Our data confirm the temporal limitation of the bone loss after complete SCI with stabilisation of BMD and geometric properties on a lower level-a finding of clinical importance considering the treatment strategies of bone loss after SCI with respect to lesion duration.


Design of admission medication reconciliation technology: a human factors approach to requirements and prototyping.
Our objectives were to (1) develop an in-depth understanding of the workflow and information flow in medication reconciliation, and (2) design medication reconciliation support technology using a combination of rapid-cycle prototyping and human-centered design. Although medication reconciliation is a national patient safety goal, limitations both of physical environment and in workflow can make it challenging to implement durable systems. We used several human factors techniques to gather requirements and develop a new process to collect a medication history at hospital admission. We completed an ethnography and time and motion analysis of pharmacists in order to illustrate the processes used to reconcile medications. We then used the requirements to design prototype multimedia software for collecting a bedside medication history. We observed how pharmacists incorporated the technology into their physical environment and documented usability issues. Admissions occurred in three phases: (1) list compilation, (2) order processing, and (3) team coordination. Current medication reconciliation processes at the hospital average 19 minutes to complete and do not include a bedside interview. Use of our technology during a bedside interview required an average of 29 minutes. The software represents a viable proof-of-concept to automate parts of history collection and enhance patient communication. However, we discovered several usability issues that require attention. We designed a patient-centered technology to enhance how clinicians collect a patient's medication history. By using multiple human factors methods, our research team identified system themes and design constraints that influence the quality of the medication reconciliation process and implementation effectiveness of new technology. Evidence-based design, human factors, patient-centered care, safety, technology.


Evaluation of calibration curve-based approaches to predict clinical inducers and noninducers of CYP3A4 with plated human hepatocytes.
Cytochrome P450 (P450) induction is often considered a liability in drug development. Using calibration curve-based approaches, we assessed the induction parameters R3 (a term indicating the amount of P450 induction in the liver, expressed as a ratio between 0 and 1), relative induction score, Cmax/EC50, and area under the curve (AUC)/F2 (the concentration causing 2-fold increase from baseline of the dose-response curve), derived from concentration-response curves of CYP3A4 mRNA and enzyme activity data in vitro, as predictors of CYP3A4 induction potential in vivo. Plated cryopreserved human hepatocytes from three donors were treated with 20 test compounds, including several clinical inducers and noninducers of CYP3A4. After the 2-day treatment, CYP3A4 mRNA levels and testosterone 6β-hydroxylase activity were determined by real-time reverse transcription polymerase chain reaction and liquid chromatography-tandem mass spectrometry analysis, respectively. Our results demonstrated a strong and predictive relationship between the extent of midazolam AUC change in humans and the various parameters calculated from both CYP3A4 mRNA and enzyme activity. The relationships exhibited with non-midazolam in vivo probes, in aggregate, were unsatisfactory. In general, the models yielded better fits when unbound rather than total plasma Cmax was used to calculate the induction parameters, as evidenced by higher R(2) and lower root mean square error (RMSE) and geometric mean fold error. With midazolam, the R3 cut-off value of 0.9, as suggested by US Food and Drug Administration guidance, effectively categorized strong inducers but was less effective in classifying midrange or weak inducers. This study supports the use of calibration curves generated from in vitro mRNA induction response curves to predict CYP3A4 induction potential in human. With the caveat that most compounds evaluated here were not strong inhibitors of enzyme activity, testosterone 6β-hydroxylase activity was also demonstrated to be a strong predictor of CYP3A4 induction potential in this assay model.


Histone deacetylase 3 (HDAC3) plays an important role in retinal ganglion cell death after acute optic nerve injury.
Optic nerve damage initiates a series of early atrophic events in retinal ganglion cells (RGCs) that precede the BAX-dependent committed step of the intrinsic apoptotic program. Nuclear atrophy, including global histone deacetylation, heterochromatin formation, shrinkage and collapse of nuclear structure, and the silencing of normal gene expression, comprise an important obstacle to overcome in therapeutic approaches to preserve neuronal function. Several studies have implicated histone deacetylases (HDACs) in the early stages of neuronal cell death, including RGCs. Importantly, these neurons exhibit nuclear translocation of HDAC3 shortly after optic nerve damage. Additionally, HDAC3 activity has been reported to be selectively toxic to neurons. RGC-specific conditional knockout of Hdac3 was achieved by transducing the RGCs of Hdac3fl/fl mice with an adeno-associated virus serotype 2 carrying CRE recombinase and GFP (AAV2-Cre/GFP). Controls included similar viral transduction of Rosa26fl/fl reporter mice. Optic nerve crush (ONC) was then performed on eyes. The ablation of Hdac3 in RGCs resulted in significant amelioration of characteristics of ONC-induced nuclear atrophy such as H4 deacetylation, heterochromatin formation, and the loss of nuclear structure. RGC death was also significantly reduced. Interestingly, loss of Hdac3 expression did not lead to protection against RGC-specific gene silencing after ONC, although this effect was achieved using the broad spectrum inhibitor, Trichostatin A. Although other HDACs may be responsible for gene expression changes in RGCs, our results indicate a critical role for HDAC3 in nuclear atrophy in RGC apoptosis following axonal injury. This study provides a framework for studying the roles of other prevalent retinal HDACs in neuronal death as a result of axonal injury.


Fatal progression of experimental visceral leishmaniasis is associated with intestinal parasitism and secondary infection by commensal bacteria, and is delayed by antibiotic prophylaxis.
Leishmania donovani causes visceral leishmaniasis (VL), which is typically fatal without treatment. There is substantial variation between individuals in rates of disease progression, response to treatment and incidence of post-treatment sequelae, specifically post-kala-azar dermal leishmaniasis (PKDL). Nevertheless, the majority of infected people are asymptomatic carriers. Hamsters and mice are commonly used as models of fatal and non-fatal VL, respectively. Host and parasite genetics are likely to be important factors, but in general the reasons for heterogeneous disease presentation in humans and animal models are poorly understood. Host microbiota has become established as a factor in cutaneous forms of leishmaniasis but this has not been studied in VL. We induced intestinal dysbiosis in mice and hamsters by long-term treatment with broad-spectrum antibiotics in their drinking water. There were no significant differences in disease presentation in dysbiotic mice. In contrast, dysbiotic hamsters infected with L. donovani had delayed onset and progression of weight loss. Half of control hamsters had a rapid progression phenotype compared with none of the ABX-treated animals and the nine-month survival rate was significantly improved compared to untreated controls (40% vs. 10%). Antibiotic-treated hamsters also had significantly less severe hepatosplenomegaly, which was accompanied by a distinct cytokine gene expression profile. The protective effect was not explained by differences in parasite loads or haematological profiles. We further found evidence that the gut-liver axis is a key aspect of fatal VL progression in hamsters, including intestinal parasitism, bacterial translocation to the liver, malakoplakia and iron sequestration, none of which occurred in non-progressing murine VL. Diverse bacterial genera were cultured from VL affected livers, of which Rodentibacter was specifically absent from ABX-treated hamsters, indicating this pathobiont may play a role in promoting disease progression. The results provide experimental support for antibiotic prophylaxis against secondary bacterial infections as an adjunct therapy in human VL patients.


Stopped-flow spectrophotometric assay of glycerol permeation in Escherichia coli: applicability and limitations.
The passive permeation and facilitated diffusion of glycerol in various strains of Escherichia coli have been studied by stopped-flow spectrophotometry. Contrary to the prediction for glycerol entry by simple diffusion, the reciprocal relaxation time (1/tau, s-1) for the passive permeation of glycerol in cells grown in the presence of glucose was not constant but decreased as the glycerol concentration increased above 100 mM. This anomaly was not due to refractive index differences or to the presence of residual levels of the glycerol facilitator protein in non-induced cells. Although reciprocal relaxation times for glycerol-induced E. coli exhibited the expected elevation relative to non-induced cells, a similar anomalous decrease 1/tar (s-1) with increasing glycerol concentration was observed. In addition, at early times after suspension in dilute buffer, the 1/tau (s-1) values obtained for induced or non-induced E. coli swelling in glycerol were considerably greater than for organisms incubated in dilute buffer for longer times. We concluded that either this spectrophotometric technique was not monitoring solely the permeation of glycerol into E. coli, or concentrations of glycerol above 100 mM significantly perturbed the structure of the E. coli cell envelope.


[Orthotopic replacement of the urinary bladder in females].
Orthotopic cystoplasty for various diseases of the urinary bladder was made in 58 females aged 22 to 78 years (mean age 52.5 +/- 5.8 years) in 1996-2005. Surgery was indicated in muscular-invasive cancer of the bladder (n = 35, 60.3%), microcystis (n = 21, 36.3%), bladder atonia (n = 1, 1.7%), vesicovaginal fistula (n = 1, 1.7%). The reservoir was made of iliac segment in 50 (86,2%) patients, of gastric body - in 8 (13.8%) patients. Postoperative complications arose in 7 (12.1%) patients, late complications occurred in 4 (6.8%). Postoperative lethality was not registered, 12 months later 3 (5.2%) patients died of cancer progressiion. Day continence after ileo- and gastrocystoplasty was 93.3 and 87.8%, night - 45.2 and 32.8%, respectively. Urodynamics was satisfactory. Chronic continence occurred in 3 (5.6%) patients. Satisfactory clinical and functional results of artificial reservoir creation in females support advantages of this method of urine derivation. Gastrocystoplasty is a promising method of urinary bladder replacement. It is important to assess function of the lower urinary tract before operation. Reservoir-vaginal fistula is a new kind of urogenital fistulas. It is treated by transvaginal fistuloraphy.


Human IL-Rbeta chains form IL-2 binding homodimers.
Two types of functional interleukin-2 receptor (IL-2Ralpha/IL-2Rbeta/gammac and IL-2Rbeta/gammac) have already been characterized in humans. Here we describe a new form consisting of IL-2Rbeta/beta homodimers that assemble spontaneously in the absence of gammac. Co-transfection of COS-7 cells with constructs expressing IL-2Rbeta chains tagged with either HA or MYC sequences results in the formation of IL-2Rbeta:HA/IL-2Rbeta:MYC complexes detectable by coimmunoprecipitation. The formation of these IL-2Rbeta:HA/IL-2Rbeta:MYC dimers is also observed in the absence of IL-2. Moreover, in COS cells expressing chimeras of IL-2Rbeta fused to fluorescence reporters such as IL-2Rbeta:ECFP and IL-2Rbeta:EYFP, we also observed specific FRET at the surface of living cells, as expected for dimer formation. Transiently transfected COS-7 cells expressing IL-2Rbeta bind 125I-labeled IL-2 (homodimers, Kd = 1nM) as cells expressing both IL-2Rbeta and gammac chains (heterodimers, Kd = 1 nM). IL-2Rbeta/IL-2Rbeta could represent either a decoy receptor or a new form of IL-2R involved in signaling when gammac expression is low.


Epigenetic regulation of autophagy in coronavirus disease 2019 (COVID-19).
The coronavirus disease 2019 (COVID-19) pandemic has become the most serious global public health issue in the past two years, requiring effective therapeutic strategies. This viral infection is a contagious disease caused by new coronaviruses (nCoVs), also called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Autophagy, as a highly conserved catabolic recycling process, plays a significant role in the growth and replication of coronaviruses (CoVs). Therefore, there is great interest in understanding the mechanisms that underlie autophagy modulation. The modulation of autophagy is a very complex and multifactorial process, which includes different epigenetic alterations, such as histone modifications and DNA methylation. These mechanisms are also known to be involved in SARS-CoV-2 replication. Thus, molecular understanding of the epigenetic pathways linked with autophagy and COVID-19, could provide novel therapeutic targets for COVID-19 eradication. In this context, the current review highlights the role of epigenetic regulation of autophagy in controlling COVID-19, focusing on the potential therapeutic implications.


Strategy repetition in young and older adults: a study in arithmetic.
We investigated a new phenomenon that sheds light on age-related differences in strategy selection: the strategy repetition phenomenon (i.e., tendency to repeat the same strategy over consecutive items). Young and older adults had to provide the best estimates of multiplication problems like 47 × 86. They had to select the best of 2 rounding strategies on each problem, the rounding-down strategy (i.e., doing 40 × 80 = 3,200) or the rounding-up strategy (i.e., doing 50 × 90 = 4,500). Data showed that both young and older adults repeated the same strategy over consecutive problems more often than chance and repeated strategies more often in the 2-prime condition (i.e., after executing one strategy to solve the 2 immediately preceding problems) than in the 1-prime condition (i.e., after executing a strategy on one immediately preceding problem). Moreover, this strategy repetition phenomenon increased with age, especially in the most difficult condition (e.g., when participants solved rounding-up problems in the 2-prime condition). Our findings have important theoretical and empirical implications for computational models of strategy selection and for furthering our understanding of strategic development during adulthood.


Breath Hydrogen Testing in East and Southeast Asia.
Breath hydrogen tests are popular, noninvasive tests for the assessment of carbohydrate fermentation in patients with irritable bowel syndrome (IBS) and functional dyspepsia (FD). There is limited information regarding the utility of breath hydrogen and methane tests in IBS and FD patients in East and Southeast Asia. This review aims to summarize current literature about common indications of breath testing in this region, the genesis of functional gastrointestinal symptoms by provocative breath testing and provide suggestions for correct use. The most common testing indication is the assessment of lactose intolerance, followed by small intestinal bacterial overgrowth (SIBO) and differentiation of intestinal gas profiles in research setting. Studies in this region not only documented a high prevalence of lactose malabsorption but a population, both healthy and IBS, that is highly symptomatic to typical lactose intakes. Breath hydrogen assessment of other fermentable carbohydrates (FODMAPs) are fairly uncommon, whereas methane breath testing is almost nonexistent. Cumulative hydrogen production following lactulose was also not excessive in IBS patients compared with controls. The evidence however, for the detection of SIBO suggests limited reliability in the use of lactulose or glucose breath testing alone and inconclusive data on its correlation with symptoms. Conversely, little has been carried out in FD. In conclusion, breath testing should be limited in the predicting patients with SIBO for directing clinical management but can be considered in the objective assessment of lactose malabsorption within a low FODMAP diet. Recommendations to improve the interpretation of breath testing in research were also provided.


Non-steroidal anti-inflammatory drugs as disease-modifying agents for Parkinson's disease: evidence from observational studies.
Neuroinflammation may play a key role in the neurodegeneration associated with Parkinson's disease (PD). Non-steroidal anti-inflammatory drugs (NSAIDs) may be beneficial in the primary and secondary prevention of PD. 1) Do NSAIDs prevent the onset of PD?2) Are NSAIDs neuroprotective in PD - do they slow the progression of disease once PD is established?3) What are the adverse effects of taking NSAIDs in PD? We searched electronic databases, including trial registers, complemented with handsearching of conference proceedings and citation searching on key articles. All searching was updated in May 2011. We contacted authors to provide additional information where necessary. For the primary prevention review, we sought primary prevention trials and observational studies (cohort and case-control studies). Participants were free of PD when exposure to NSAIDs was assessed. For the secondary prevention review, we sought clinical trials in patients with a well-defined definition of PD. Two people independently selected studies for inclusion using predetermined criteria. Two review authors abstracted data from the source papers and assessed methodological quality independently. No studies met the inclusion criteria for the secondary prevention review. For the primary prevention review only observational studies were found. We combined data where appropriate using the inverse variance method. We assessed methodological quality using the Newcastle Ottawa Scales and by examining the period of exposure assessed prior to PD onset (or the index date in controls). Fourteen observational studies met the inclusion criteria for the primary prevention review (five cohort, nine case-control studies). Exposure to any NSAIDs or aspirin had no effect on the risk of developing PD. Exposure to non-aspirin NSAIDs reduced the risk of developing PD by 13% (effect estimate 0.87 (95% CI 0.73 to 1.04 - random-effects model), but this did not reach statistical significance. We found similar results for the most robust studies. Ibuprofen in isolation was examined in four studies and was associated with a 27% reduction in risk (effect estimate 0.73, 95% CI 0.63 to 0.85). There was a lack of information on adverse effects. There is currently no evidence for the use of NSAIDs in the secondary prevention of PD. Non-aspirin NSAIDs, particularly ibuprofen, may reduce the risk of developing PD. However, little is known of the effects of other individual drugs and at present no recommendations can be made regarding their use in primary prevention.


[Mechanism of the maintenance of the infective capacity of soil in a natural focus of leptospirosis].
The radioisotope modeling of the processes of the release of leptospires into the soil and the daily measurements of the radiation doses revealed that leptospires were regularly added by individual carriers, as well as by a group of carriers, into common infected spots on the territory of the infection focus. The frequency with which leptospires were added by a carrier into different infected spots varied: during 7 days leptospires were added 7 times and more into 16% of the spots, up to 5 times into 49% of the spots; into 35% of the spots no leptospires were added. The microscopic and bacteriological methods of investigation demonstrated that the regular release of leptospires into the infected spots resulted in maintaining the concentration of leptospires at such spots and their infective capacity. The number and distribution of these spots determined the stability of the epizootic potential of the territory.


Investigation of measurement accuracy of factors used for detective quantum efficiency measurement in digital radiography.
In the detective quantum efficiency (DQE) evaluation of detectors for digital radiography (DR) systems, physical image quality indices such as modulation transfer function (MTF) and normalized noise power spectrum (NNPS) need to be accurately measured to obtain highly accurate DQE evaluations. However, there is a risk of errors in these measurements. In this study, we focused on error factors that should be considered in measurements using clinical DR systems. We compared the incident photon numbers indicated in IEC 62220-1 with those estimated using a Monte Carlo simulation based on X-ray energy spectra measured employing four DR systems. For NNPS, influences of X-ray intensity non-uniformity, tube voltage and aluminum purity were investigated. The effects of geometric magnifications on MTF accuracy were also examined using a tungsten edge plate at distances of 50, 100 and 150 mm from the detector surface at a source-image receptor distance of 2000 mm. The photon numbers in IEC 62220-1 coincided with our estimates of values, with error rates below 2.5%. Tube voltage errors of approximately ±5 kV caused NNPS errors of within 1.0%. The X-ray intensity non-uniformity caused NNPS errors of up to 2.0% at the anode side. Aluminum purity did not affect the measurement accuracy. The maximum MTF reductions caused by geometric magnifications were 3.67% for 1.0-mm X-ray focus and 1.83% for 0.6-mm X-ray focus.