Free range hens use the range more when the outdoor environment is enriched.
To evaluate the role of using forage, shade and shelterbelts in attracting birds into the range, three trials were undertaken with free range layers both on a research facility and on commercial farms. Each of the trials on the free range research facility in South Australia used a total of 120 laying hens (Hyline Brown). Birds were housed in an eco-shelter which had 6 internal pens of equal size with a free range area adjoining the shelter. The on-farm trials were undertaken on commercial free range layer farms in the Darling Downs in Southeast Queensland with bird numbers on farms ranging from 2,000-6,800 hens. The first research trial examined the role of shaded areas in the range; the second trial examined the role of forage and the third trial examined the influence of shelterbelts in the range. These treatments were compared to a free range area with no enrichment. Aggressive feather pecking was only observed on a few occasions in all of the trials due to the low bird numbers housed. Enriching the free range environment attracted more birds into the range. Shaded areas were used by 18% of the hens with a tendency (p = 0.07) for more hens to be in the paddock. When forage was provided in paddocks more control birds (55%) were observed in the range in morning than in the afternoon (30%) while for the forage treatments 45% of the birds were in the range both during the morning and afternoon. When shelterbelts were provided there was a significantly (p<0.05) higher % of birds in the range (43% vs. 24%) and greater numbers of birds were observed in areas further away from the poultry house. The results from the on-farm trials mirrored the research trials. Overall 3 times more hens used the shaded areas than the non shaded areas, with slightly more using the shade in the morning than in the afternoon. As the environmental temperature increased the number of birds using the outdoor shade also increased. Overall 17 times more hens used the shelterbelt areas than the control areas, with slightly more using the shelterbelts in the afternoon than in the morning. Approximately 17 times more birds used the forage areas compared to the control area in the corresponding range. There were 8 times more birds using a hay bale enriched area compared to the area with no hay bales. The use of forage sources (including hay bales) were the most successful method on-farm to attract birds into the range followed by shelterbelts and artificial shade. Free range egg farmers are encouraged to provide pasture, shaded areas and shelterbelts to attract birds into the free range.


The Eternal Debate With a Consistent Answer: CABG vs PCI.
An ongoing debate exists over the role of percutaneous coronary intervention and coronary artery bypass grafting for revascularization in patients with multivessel or left main disease. Despite improvements in stent technology, bypass surgery still provides the best long-term results in the majority of patients. The present review focuses on randomized controlled trials and a meta-analysis published over the last 4 years.


Application of Intrawound Vancomycin Powder during Spine Surgery in a Patient with Dialysis-Dependent Renal Failure.
Surgical site infections (SSIs) after spinal surgery are a serious complication that can be minimized with prophylaxis. Vancomycin is a common agent used in the prevention of SSI. Given that vancomycin is renally cleared, its use requires careful observation in dialysis-dependent patients due to toxicity at supratherapeutic levels. Since minimum inhibitory concentrations (MICs) for vancomycin have increased due to the emergence of resistant pathogens, the use of vancomycin in such patients is further complicated. Local instillation of vancomycin powder is thought to provide additional protection against SSI and have lower systemic absorption. We present a patient with end-stage renal disease that developed progressively debilitating cervical spondylotic myelopathy necessitating multilevel laminectomy and instrumented fusion. Prior to closure, 1 gram of vancomycin powder was sprinkled into the surgical incision. Postoperative serum vancomycin levels were well below those associated with nephrotoxicity and ototoxicity. Based on this experience, we reviewed the relevant guidelines that were designed to prevent postoperative infections in such dialysis-dependent patients. Intrawound application of vancomycin may be a legitimate and safe option for SSI prophylaxis in patients with renal failure on dialysis.


Pattern separation in the dentate gyrus and CA3 of the hippocampus.
Theoretical models have long pointed to the dentate gyrus as a possible source of neuronal pattern separation. In agreement with predictions from these models, we show that minimal changes in the shape of the environment in which rats are exploring can substantially alter correlated activity patterns among place-modulated granule cells in the dentate gyrus. When the environments are made more different, new cell populations are recruited in CA3 but not in the dentate gyrus. These results imply a dual mechanism for pattern separation in which signals from the entorhinal cortex can be decorrelated both by changes in coincidence patterns in the dentate gyrus and by recruitment of nonoverlapping cell assemblies in CA3.


Enhanced in vitro induced production of interleukin 10 by peripheral blood mononuclear cells in rheumatoid arthritis is associated with clinical response to methotrexate treatment.
To investigate the effect of in vivo treatment with methotrexate (MTX) on the regulation of ex vivo interleukin 10 (IL-10) production by peripheral blood mononuclear cells (PBMC) derived from patients with rheumatoid arthritis (RA). Spontaneous as well as lipopolysaccharide (LPS) and phytohemagglutinin (PHA) induced IL-10 release was assessed by a specific immunoassay in culture supernatants of PBMC derived from 32 patients with active RA before and 6, 12, and 24 weeks after MTX treatment. IL- 10 production was correlated to the clinical response. As a control, IL-10 release from PBMC of 7 healthy blood donors was determined. PBMC of patients with RA showing > 50% improvement of the Paulus index after 3 and 6 months of MTX treatment (responders; n = 18) exhibited significantly enhanced IL-10 production after in vitro stimulation with LPS, whereas constitutively released IL-10 was below the detection limit of the immunoassay in all patients and controls. In contrast, IL-10 release from LPS stimulated PBMC of RA patients who showed < 20% improvement by Paulus index (nonresponders; n = 14) or who even deteriorated compared to baseline disease activity was markedly downregulated during MTX treatment in vivo. PHA-induced IL-10 release from PBMC in vitro was not significantly affected by MTX in vivo whether RA patients responded or not to MTX. Enhanced ex vivo LPS induced IL-10 production by PBMC of patients with RA is associated with a favorable therapeutic response to MTX treatment, whereas reduced production coincides more closely with disease deterioration or insufficient response. This may reflect both disease outcome upon treatment and/or the mode of the antiinflammatory action of MTX in RA. Because the LPS--but not the PHA--induced ex vivo IL-10 production by PBMC was stimulated by MTX in vivo, monocytes seem to be the prominent target cells for this drug mediated antiinflammatory cytokine regulation.


Osteopontin: possible role in prostate cancer progression.
Human prostate cancer has the propensity to metastasize to the bone where reciprocal cellular interactions between prostate cancer and bone cells are known to occur. Osteopontin (OPN), a noncollagenous bone extracellular matrix, is a secreted adhesive glycoprotein with a functional RGD cell-binding domain that interacts with the alpha(v)beta3 cell surface integrin heterodimer. OPN has been associated with malignant transformation as well as being ligand to the CD44 receptor. Polyclonal antibodies to human OPN (hOPN) were prepared, and specificity was shown by preabsorption with recombinant hOPN. The stimulatory effect of hOPN protein and the inhibitory effect of hOPN antibody on human prostate cancer cell lines LNCaP and C4-2 were assessed by induction or inhibition of anchorage-independent growth, respectively. Expression of hOPN mRNA in prostate cancer cell lines and human prostate cancer tissue specimens were measured by mRNA blot analysis. Protein expression was assessed by immunohistochemistry in human prostate cancer specimens and by Western blot analysis in prostate cancer cell lines. hOPN stimulated anchorage-independent growth of the human prostate cancer cell lines LNCaP and C4-2 in vitro. Antibodies to hOPN inhibited the growth-stimulatory effect by endogenous OPN, which can be overcome by the addition of exogenous hOPN. hOPN mRNA and protein are expressed in human prostate cancer cell lines in vitro and in clinical human prostate cancer specimens. These findings taken together suggest that OPN may act as a paracrine and autocrine mediator of prostate cancer growth and progression.


Two crystal structures of Escherichia coli N-acetyl-L-glutamate kinase demonstrate the cycling between open and closed conformations.
N-Acetyl-L-glutamate kinase (NAGK), the paradigm enzyme of the amino acid kinase family, catalyzes the second step of arginine biosynthesis. Although substrate binding and catalysis were clarified by the determination of four crystal structures of the homodimeric Escherichia coli enzyme (EcNAGK), we now determine 2 A resolution crystal structures of EcNAGK free from substrates or complexed with the product N-acetyl-L-glutamyl-5-phosphate (NAGP) and with sulfate, which reveal a novel, very open NAGK conformation to which substrates would associate and from which products would dissociate. In this conformation, the C-domain, which hosts most of the nucleotide site, rotates approximately 24 degrees -28 degrees away from the N-domain, which hosts the acetylglutamate site, whereas the empty ATP site also exhibits some changes. One sulfate is found binding in the region where the beta-phosphate of ATP normally binds, suggesting that ATP is first anchored to the beta-phosphate site, before perfect binding by induced fit, triggering the shift to the closed conformation. In contrast, the acetylglutamate site is always well formed, although its beta-hairpin lid is found here to be mobile, being closed only in the subunit of the EcNAGK-NAGP complex that binds NAGP most strongly. Lid closure appears to increase the affinity for acetylglutamate/NAGP and to stabilize the closed enzyme conformation via lid-C-domain contacts. Our finding of NAGP bound to the open conformation confirms that this product dissociates from the open enzyme form and allows reconstruction of the active center in the ternary complex with both products, delineating the final steps of the reaction, which is shown here by site-directed mutagenesis to involve centrally the invariant residue Gly11.


Temporal view of the costs and benefits of self-deception.
Researchers have documented many cases in which individuals rationalize their regrettable actions. Four experiments examine situations in which people go beyond merely explaining away their misconduct to actively deceiving themselves. We find that those who exploit opportunities to cheat on tests are likely to engage in self-deception, inferring that their elevated performance is a sign of intelligence. This short-term psychological benefit of self-deception, however, can come with longer-term costs: when predicting future performance, participants expect to perform equally well-a lack of awareness that persists even when these inflated expectations prove costly. We show that although people expect to cheat, they do not foresee self-deception, and that factors that reinforce the benefits of cheating enhance self-deception. More broadly, the findings of these experiments offer evidence that debates about the relative costs and benefits of self-deception are informed by adopting a temporal view that assesses the cumulative impact of self-deception over time.


Efficacy of rituximab treatment for thyroid-associated ophthalmopathy as a result of intraorbital B-cell depletion in one patient unresponsive to steroid immunosuppression.
One patient with Graves' hyperthyroidism and ophthalmopathy in its active phase and unresponsive to steroid, was treated with the anti-CD20 monoclonal antibody, rituximab (RTX), as part of an open study. The effect of RTX in the thyroid and the orbital tissues was studied. The ophthalmopathy responded to RTX therapy by ameliorating the eye signs with a decrease in the clinical activity score from 5 to 2 in 3 months, while the patient had peripheral B-cell depletion. Hyperthyroidism did not improve during the 6 months of B-cell depletion and serum TSH-receptor antibodies (TRAb) levels did not significantly change after RTX therapy. Therefore, the patient underwent total thyroidectomy and few B-cells were found in the thyroid tissue specimens. While the patient eye disease remained stable (clinical activity score = 2), we performed corrective orbital decompression and we found absence of lymphocytes in the orbital tissue specimens. We believe that RTX treatment in Graves' disease may cause amelioration of ophthalmopathy by depleting total lymphocytes population in the orbit. The persistence of Graves' hyperthyroidism suggests that a single cycle of RTX does not result in complete lymphocyte depletion in thyroid tissue and thus no decline in serum TRAb was observed.


Left ventricular apical ballooning syndrome after pacemaker implantation in a male.
Left apical ballooning syndrome, also known as Takotsubo cardiomyopathy (TTC), characterized by transient left ventricular dysfunction is increasingly recognized worldwide. Predominantly affecting females, this condition mimics myocardial infarction and often occurs in the setting of emotional or physical stress. We report the case of a 77-year-old male who was admitted to the hospital for complete heart block and developed TTC after pacemaker implantation. To our knowledge, this is the first report of TTC development after pacemaker implantation in a male.


Salivary cortisol, salivary alpha amylase, and the dental anxiety scale.
The aim of this study was to investigate the correlation between dental anxiety, salivary cortisol, and salivary alpha amylase (sAA) levels. Furthermore, the aim was to look into individual differences such as age, race, gender, any existing pain, or traumatic dental experience and their effect on dental anxiety. This study followed a cross-sectional design and included a convenience sample of 46. Every patient was asked to complete the Dental Anxiety Scale (DAS) and a basic demographic/dental history questionnaire. A saliva sample, utilizing the method of passive drooling, was then collected in 2-mL cryovials. Samples were analyzed for salivary cortisol and sAA levels by Salimetrics. Significant associations were observed between DAS scores and presence of pain and history of traumatic dental experience. However, no significant correlations were observed between DAS, cortisol, and sAA levels. Our study reconfirms that dental anxiety is associated with presence of pain and a history of traumatic dental experience. On the other hand, our study was the first to our knowledge to test the correlation between the DAS and sAA; nevertheless, our results failed to show any significant correlation between dental anxiety, cortisol, and sAA levels.


Modulation of coactivator recruitment by cooperative ligand binding to human Estrogen receptor alpha and beta.
Estrogen receptor (ER) is a member of the nuclear receptor superfamily, and functions as a ligand-dependent transcription factor with roles in cell growth and differentiation. In addition to endogenous estrogen, 17beta-estradiol (E(2)) and artificial antagonists, many suspected environmental estrogenic chemicals are reported to bind to ER, with various affinities and transcriptional responses. ER is also an allosteric protein and shows a positive cooperative interaction with E(2). Cooperativity affects inter-subunit interaction, and while ligand-bound ER interacts with coactivators, antagonist-bound ER does not. We therefore hypothesized that ligand-binding characteristics influence coactivator recruitment to the ER dimer, and thereby affect transcriptional activity. We investigated the interaction between ER and human Steroid Receptor Coactivator-1 (SRC-1), in the presence of compounds exhibiting various Hill coefficients. In the case of both ER subtypes (ERalpha and ERbeta), the Hill coefficients of the compounds tested correlated with the affinity of the ER-ligand complex to SRC-1, with the exception of ERbeta-4-n-nonylphenol and ER-antagonist complexes. This is the first report to investigate the relationship between Hill coefficients of ligand binding and coactivator interaction with the ER-ligand complex. We also examined the proteolytic digestion of ER using trypsin, in the presence and absence of compounds with various Hill coefficients, to investigate ligand-dependent conformational changes in ER. We used not only agonists and antagonists but also compounds of weak biological activity (partial agonists). Our results shed light on the subtle modulation of transcriptional activation by chemical agents.


Public response to cost-quality tradeoffs in clinical decisions.
To explore public attitudes toward the incorporation of cost-effectiveness analysis into clinical decisions. The authors presented 781 jurors with a survey describing 1 of 6 clinical encounters in which a physician has to choose between cancer screening tests. They provided cost-effectiveness data for all tests, and in each scenario, the most effective test was more expensive. They instructed respondents to imagine that he or she was the physician in the scenario and asked them to choose which test to recommend and then explain their choice in an open-ended manner. The authors then qualitatively analyzed the responses by identifying themes and developed a coding scheme. Two authors separately coded the statements with high overall agreement (kappa = 0.76). Categories were not mutually exclusive. Overall, 410 respondents (55%) chose the most expensive option, and 332 respondents (45%) choose a less expensive option. Explanatory comments were given by 82% respondents. Respondents who chose the most expensive test focused on the increased benefit (without directly acknowledging the additional cost) (39%), a general belief that life is more important than money (22%), the significance of cancer risk for the patient in the scenario (20%), the belief that the benefit of the test was worth the additional cost (8%), and personal anecdotes/preferences (6%). Of the respondents who chose the less expensive test, 40% indicated that they did not believe that the patient in the scenario was at significant risk for cancer, 13% indicated that they thought the less expensive test was adequate or not meaningfully different from the more expensive test, 12% thought the cost of the test was not worth the additional benefit, 9% indicated that the test was too expensive (without mention of additional benefit), and 7% responded that resources were limited. Public response to cost-quality tradeoffs is mixed. Although some respondents justified their decision based on the cost-effectiveness information provided, many focused instead on specific features of the scenario or on general beliefs about whether cost should be incorporated into clinical decisions.


Familial carpal tunnel syndrome in three generations of a black family.
This is a report of familial carpal tunnel syndrome (CTS) occurring in seven members of three generations of a black family. Two of the cases had associated flexor tendonitis with trigger finger symptoms. Twenty members of four generations had nerve conduction studies. The age of those affected by CTS ranged from 29 to 67 years of age. Two subjects to date required bilateral CTS surgical releases. The familial CTS appears to have an autosomal dominant pattern of CTS inheritance with high penetrance. This is believed to be the first report of familial CTS in a black family.


Prolactin and growth hormone stimulation of lactation in mice requires thyroid hormones.
This experiment tested the hypothesis that thyroid hormones are essential for a milk production response to growth hormone (GH) and prolactin (PRL). Prior to breeding, female transgenic mice expressing the herpes simplex type-I thymidine kinase in the thyroid were treated with ganciclovir to ablate thyroid follicular cells. To provide for normal gestation, thyrocyte-ablated mice were supplied thyroxine (T4) in drinking water (0.2 microgram/ml) until 7 days before parturition. Litter size was adjusted to 9 pups, hormone administration began on Day 2 of lactation, and mice were sacrificed on Day 12. There were 5-6 mice in each of 7 treatments that included nonablated controls, thyrocyte-ablated controls, and thyrocyte-ablated mice treated with T4, GH, PRL, GH + T4, and PRL + T4. Thyroxine was administered in drinking water, and GH and PRL (20 microgram/d) were administered by subcutaneous injection. Compared with thyrocyte-ablated controls, litter weight gain was unaffected when dams were treated with GH, PRL, or T4 alone. However, when dams were treated with GH or PRL in combination with T4, litter weight gain increased 13% compared with thyrocyte-ablated controls and 18% compared with GH or PRL-treated mice. Concentration of T4 in serum of pups averaged 62 ng/ml and did not differ among treatments. Concentration of T4 in serum of dams averaged 76 ng/ml when T4-treated. Thyroxine 5'-deiodinase (5'D), the enzyme that converts T4 to triiodothyronine, was quantitated in liver, kidney, and mammary gland. Quantity of 5'D was lower in liver and kidney of thyrocyte-ablated dams without T4 than in respective tissues of mice treated with T4, and there was no effect of GH or PRL. However, in mammary gland, 5'D was increased by treatment with GH, PRL, or T4. Data show that thyroid hormones are necessary for a galactopoietic response to GH and PRL and demonstrate a unique organ-specific regulation of 5'D by galactopoietic hormones.


The influence of respiratory motion on dose delivery in a mouse lung tumour irradiation using the 4D MOBY phantom.
During precision irradiation of a preclinical lung tumour model, the tumour is subject to breathing motion and it can partially move out of the irradiation field. This work aimed to perform a quantitative analysis of the impact of respiratory motion on a mouse lung tumour irradiation with small fields. A four-dimensional digital mouse whole body phantom (MOBY) with a virtual 4-mm spherical lung tumour at different locations in both lungs is used to simulate a breathing anaesthetized mouse in different breathing phases representing a full breathing cycle. The breathing curve is determined by fluoroscopic imaging of an anaesthetized mouse. Each MOBY time frame is loaded in a dedicated treatment planning system (small animal radiotherapy-Plan) and is irradiated by a full arc with a 5-mm circular collimator. Mean and time-dependent organ doses are calculated for the tumour, heart and spinal cord. Depending on the location of the lung tumour, an overestimation of the mean tumour dose up to 11% is found. The mean heart dose could be both overestimated or underestimated because the heart moves in or out of the irradiation field depending on the beam target location. The respiratory motion does not affect the mean spinal cord dose. A dose gradient is visible in the time-dependent tumour dose distribution. In the future, new methods need to be developed to track the lung tumour motion before preclinical irradiation to adjust the irradiation plan. Margins, collimator diameter and target dose could be changed easily, but they all have their drawbacks. State-of-the-art clinical techniques such as respiratory gating or motion tracking may offer a solution for the cold spots in the time-dependent tumour dose. Advances in knowledge: A suitable method is found to quantify changes in organ dose due to respiratory motion in mouse lung tumour image-guided precision irradiation.


Epidemiology, prevention, screening, diagnosis, and evaluation: update of the ICUD-SIU joint consultation on bladder cancer.
To update current recommendations on prevention, screening, diagnosis, and evaluation of bladder cancer (BC) based on a thorough assessment of the most recent literature on these topics. A non-systematic review was performed, including articles until June 2017. A variety of original articles, reviews, and editorials were selected according to their epidemiologic, demographic, and clinical relevance. Assessment of the level of evidence and grade of recommendations was performed according to the International Consultation on Urological Diseases grading system. BC is the ninth most common cancer worldwide with 430,000 new cases in 2012. Currently, approximately 165,000 people die from the disease annually. Absolute incidence and prevalence of BC are expected to rise significantly during the next decades because of population ageing. Tobacco smoking is still the main risk factor, accounting for about 50% of cases. Smoking cessation is, therefore, the most relevant recommendation in terms of prevention, as the risk of developing BC drops almost 40% within 5 years of cessation. BC screening is not recommended for the general population. BC diagnosis remains mainly based on cystoscopy, but development of new endoscopic and imaging technologies may rapidly change the diagnosis algorithm. The same applies for local, regional, and distant staging modalities. A thorough understanding of epidemiology, risk factors, early detection strategies, diagnosis, and evaluation is essential for correct, evidence-based management of BC patients. Recent developments in endoscopic techniques and imaging raise the hope for providing better risk-adopted approaches and thereby improving clinical outcomes.


Impact of JPEG 2000 compression on deep convolutional neural networks for metastatic cancer detection in histopathological images.
The availability of massive amounts of data in histopathological whole-slide images (WSIs) has enabled the application of deep learning models and especially convolutional neural networks (CNNs), which have shown a high potential for improvement in cancer diagnosis. However, storage and transmission of large amounts of data such as gigapixel histopathological WSIs are challenging. Exploiting lossy compression algorithms for medical images is controversial but, as long as the clinical diagnosis is not affected, is acceptable. We study the impact of JPEG 2000 compression on our proposed CNN-based algorithm, which has produced performance comparable to that of pathologists and which was ranked second place in the CAMELYON17 challenge. Detecting tumor metastases in hematoxylin and eosin-stained tissue sections of breast lymph nodes is evaluated and compared with the pathologists' diagnoses in three different experimental setups. Our experiments show that the CNN model is robust against compression ratios up to 24:1 when it is trained on uncompressed high-quality images. We demonstrate that a model trained on lower quality images-i.e., lossy compressed images-depicts a classification performance that is significantly improved for the corresponding compression ratio. Moreover, it is also observed that the model performs equally well on all higher-quality images. These properties will help to design cloud-based computer-aided diagnosis (CAD) systems, e.g., telemedicine that employ deep CNN models that are more robust to image quality variations due to compression required to address data storage and transmission constraints. However, the results presented are specific to the CAD system and application described, and further work is needed to examine whether they generalize to other systems and applications.


Histamine: neural circuits and new medications.
Histamine was first identified in the brain about 50 years ago, but only in the last few years have researchers gained an understanding of how it regulates sleep/wake behavior. We provide a translational overview of the histamine system, from basic research to new clinical trials demonstrating the usefulness of drugs that enhance histamine signaling. The tuberomammillary nucleus is the sole neuronal source of histamine in the brain, and like many of the arousal systems, histamine neurons diffusely innervate the cortex, thalamus, and other wake-promoting brain regions. Histamine has generally excitatory effects on target neurons, but paradoxically, histamine neurons may also release the inhibitory neurotransmitter GABA. New research demonstrates that activity in histamine neurons is essential for normal wakefulness, especially at specific circadian phases, and reducing activity in these neurons can produce sedation. The number of histamine neurons is increased in narcolepsy, but whether this affects brain levels of histamine is controversial. Of clinical importance, new compounds are becoming available that enhance histamine signaling, and clinical trials show that these medications reduce sleepiness and cataplexy in narcolepsy.


Plasmodium falciparum gametocytes from culture in vitro develop to sporozoites that are infectious to primates.
Gametocytes of two strains of the human malaria parasite Plasmodium falciparum have been produced in high density by means of a continuous-flow cultivation system. The gametocytes of these two strains infected a mean of 36 percent and 71 percent, respectively, of Anopheles freeborni mosquitoes that fed on a suspension of red blood cells containing the culture gametocytes. Sporozoites harvested from the infected mosquito salivary glands were infective to the chimpanzee (Pan troglodytes) and the owl monkey (Aotus trivirgatus).


Neighborhood Environment Perceptions among Latinos in the U.S.
In the U.S., immigrants and racial/ethnic minorities (e.g., Latinos) often report unfavorable neighborhood environments, which may hinder physical activity (PA). Among Latinos, PA levels are disproportionately lower in foreign-born, female, older, and low-education individuals. It is unclear whether these subgroups, including those from multiple disadvantaged backgrounds (e.g., low education, foreign-born), perceive worse neighborhood environments for PA. This cross-sectional study aimed to examine differences in neighborhood environment perceptions among Latinos in the 2015 National Health Interview Survey (N = 4643; 59% foreign-born). Logistic regression models examined nativity-and its interactions with age, gender, and education-in relation to the perceived presence of transportation infrastructure (two items) and destinations (four items), controlling for self-reported walking. Models used sample weights and accounted for the complex survey design. Nativity was not significantly associated with neighborhood environment perceptions. However, nativity interactions with age and education showed the greatest inequities (lowest perceptions) of neighborhood infrastructure (e.g., fewer sidewalks) or destinations (e.g., fewer places to relax) among disadvantaged U.S.-born (older or low education) and advantaged foreign-born (higher education) Latinos. Findings suggest neighborhood perceptions are shaped by complex interactions of nativity with structural (education) and contextual (age) factors. Additional research is needed to complement our findings and inform environmental interventions targeting Latinos.


Comparison of drug-susceptibility patterns and gene sequences associated with clarithromycin and azithromycin resistance in Mycobacterium abscessus complex isolates and evaluation of the accumulation of intrinsic macrolide resistance.
Introduction. Mycobacterium abscessus complex (MABC) is an infectious agent associated with macrolide resistance and treatment failure.Hypothesis/Gap Statement. Despite drug-susceptibility testing for MABC isolates including clarithromycin (CAM), long-term treatment with azithromycin (AZM) for MABC disease is recommended.Aim. We compared phenotypic and genotypic resistance to AZM and CAM in clinical isolates and evaluated the accumulation of intrinsic macrolide resistance (AIM) and morphological changes by macrolides exposure.Methodology. Forty-nine isolates were characterized regarding erm(41) sequevars. Sequencing data were compared to the nucleotide sequence of rrl and whiB7. The AIM MIC was performed in three reference strains and 15 isolates were randomized [each set of five isolates with M. abscessus subsp. abscessus (MAA) T28, MAA C28 and subsp. massiliense (MAM)].Results. The 49 isolates were distributed as 24 MAA T28, 5 MAA C28 and 20 MAM. The MIC50 values to CAM at day 3 in MAA T28, C28 and MAM were 1, 0.12 and 0.12 µg ml-1, while those at day 14 were 32, 0.5 and 0.12 µg ml-1, respectively. The AZM-MIC50 values at day 3 of the above isolates were 4, 0.25 and 0.5 µg ml-1, while those at day 14 were >64, 0.5 and 0.5 µg ml-1, respectively. Neither mutations in rrl of MAA T28 with acquired resistance nor deletions in whiB7 of MAA T28 without inducible resistance were observed . For AIM MIC, MAA T28 showed that the time-to-detection of AZM resistance was significantly faster over that of CAM (P<0.05). Morphological changes were not determined in all isolates.Conclusion. Our findings did not support the suggestion for the preferential use of AZM for, at least, MAA T28 disease due to the high-level MIC value and the increased AIM. The long duration of AZM-based treatment eventually may favour the emergence of isolates with a high-level of intrinsic resistance.


Tryptophan 5-hydroxylase in rat intestine.
Tryptophan 5-hydroxylase was partially purified from rat small intestine and characterized. The enzyme activity was mainly localized in the distal one-fourth of the small intestine. The enzyme required Fe(2+), 2-amino-4-hydroxy-6,7-dimethyl-5,6,7,8-tetrahydropteridine and oxygen for full activity. The pH optimum of the reaction was 8.0. The hydroxylation rate of d-tryptophan by the enzyme was one-third that of l-tryptophan. l-Phenylalanine and l-tyrosine could not serve as substrates. The physiological significance of the enzyme is discussed.


Evaluation of the 'Empathic Care of a Vulnerable Older Person' e-simulation.
Healthcare reports have identified that the nursing care provided to frail older people is sometimes indifferent, unkind, and lacking in empathy. Compelling research indicates that these types of healthcare interactions can result in both emotional and physiological harm. Thus, there is a need for authentic learning experiences that enhance nursing students' empathy towards older people and that they can reflect upon, learn from and transfer to their real-world practice. e-Simulations provide a pragmatic way of addressing this need. The aim of this study was to evaluate the impact of an 'Empathic Care of a Vulnerable Older Person' e-simulation on nursing students' empathy levels. A convenience sample of first year nursing students from one university in the United Kingdom and two Australian universities was recruited for the study. A three-group pre-post study was conducted using the Comprehensive State Empathy Scale to evaluate the impact of the effectiveness of the e-simulation. Sample characteristics were summarised using descriptive statistics. Dependent t-tests and analysis of variance (ANOVA) were used to compare the changes in empathy scores pre post and differences between groups. A total of 684 nursing students participated in the study; their average age was 23 years. Overall, there was a significant increase in empathy scores from pre-test to post-test. Post-hoc comparison of the three groups indicated that the e-simulation had a greater impact on the empathy levels of participants from Universities 2 and 3, compared to those from University 1. e-Simulations using narrative methodologies that cater for learners' emotional memory appear to be an effective approach for enhancing empathy towards older people. However, further studies are needed to explore how this learning activity might inform and influence learners' future clinical practice.


Nutrient-driven O-GlcNAc cycling - think globally but act locally.
Proper cellular functioning requires that cellular machinery behave in a spatiotemporally regulated manner in response to global changes in nutrient availability. Mounting evidence suggests that one way this is achieved is through the establishment of physically defined gradients of O-GlcNAcylation (O-linked addition of N-acetylglucosamine to serine and threonine residues) and O-GlcNAc turnover. Because O-GlcNAcylation levels are dependent on the nutrient-responsive hexosamine signaling pathway, this modification is uniquely poised to inform upon the nutritive state of an organism. The enzymes responsible for O-GlcNAc addition and removal are encoded by a single pair of genes: both the O-GlcNAc transferase (OGT) and the O-GlcNAcase (OGA, also known as MGEA5) genes are alternatively spliced, producing protein variants that are targeted to discrete cellular locations where they must selectively recognize hundreds of protein substrates. Recent reports suggest that in addition to their catalytic functions, OGT and OGA use their multifunctional domains to anchor O-GlcNAc cycling to discrete intracellular sites, thus allowing them to establish gradients of deacetylase, kinase and phosphatase signaling activities. The localized signaling gradients established by targeted O-GlcNAc cycling influence many important cellular processes, including lipid droplet remodeling, mitochondrial functioning, epigenetic control of gene expression and proteostasis. As such, the tethering of the enzymes of O-GlcNAc cycling appears to play a role in ensuring proper spatiotemporal responses to global alterations in nutrient supply.


Repeated evolutionary transitions of flavobacteria from marine to non-marine habitats.
The taxonomy of marine and non-marine organisms rarely overlap, but the mechanisms underlying this distinction are often unknown. Here, we predicted three major ocean-to-land transitions in the evolutionary history of Flavobacteriaceae, a family known for polysaccharide and peptide degradation. These unidirectional transitions were associated with repeated losses of marine signature genes and repeated gains of non-marine adaptive genes. This included various Na+ -dependent transporters, osmolyte transporters and glycoside hydrolases (GH) for sulfated polysaccharide utilization in marine descendants, and in non-marine descendants genes for utilizing the land plant material pectin and genes facilitating terrestrial host interactions. The K+ scavenging ATPase was repeatedly gained whereas the corresponding low-affinity transporter repeatedly lost upon transitions, reflecting K+ ions are less available to non-marine bacteria. Strikingly, the central metabolism Na+ -translocating NADH: quinone dehydrogenase gene was repeatedly gained in marine descendants, whereas the H+ -translocating counterpart was repeatedly gained in non-marine lineages. Furthermore, GH genes were depleted in isolates colonizing animal hosts but abundant in bacteria inhabiting other non-marine niches; thus relative abundances of GH versus peptidase genes among Flavobacteriaceae lineages were inconsistent with the marine versus non-marine dichotomy. We suggest that phylogenomic analyses can cast novel light on mechanisms explaining the distribution and ecology of key microbiome components.


Polarized infrared emission using frequency selective surfaces.
An emission frequency selective surface, or eFSS, is made up of a periodic arrangement of resonant antenna structures above a ground plane. By exploiting the coupling and symmetry properties of an eFSS, it is possible to introduce polarization sensitive thermal emission and, subsequently, coherent emission. Two surfaces are considered: a linearly polarized emission surface and a circularly polarized emission surface. The linearly polarized surface consisted of an array of dipole elements and measurements demonstrate these surfaces can be fabricated into high polarization contrast patterns. The circularly polarized surface required the use of an asymmetrical tripole element to maintain coherence between orthogonal current modes and introduce the necessary phase delay to realize circularly polarized radiation.


Protection against amebic liver abscess in hamsters by means of immunization with amebic antigen and some of its fractions.
Immunization of hamsters by intramuscular injections of an amebic extract and of two of its fractions, emulsified with complete Freund's adjuvant, resulted in protection against the development of amebic liver abscess, following intrahepatic inoculation of axenic trophozoites of Entamoeba histolytica such that Fraction I, Fraction II, and the whole antigen conferred protection to 18 out of 18, 4 out of 18, and 11 out of 18 hamsters, respectively. Splenomegaly was found to accompany the development of hepatic liver abscesses in this experimental system. There was a very high degree of correlation (r = 0.95) between the weights of the abscesses and the spleens. On the other hand, there was no correlation between the anti-amebic antibody titers (determined by the indirect hemagglutination test) and the development of the liver abscesses within the time-span of the experimental protocol used in this study.


Veterinarians and public practice at the Virginia-Maryland Regional College of Veterinary Medicine: building on a tradition of expertise and partnership.
The Virginia-Maryland Regional College of Veterinary Medicine (VMRCVM), a regional veterinary college for Maryland and Virginia, has a long and unique tradition of encouraging careers in public and corporate veterinary medicine. The VMRCVM is home to the Center for Public and Corporate Veterinary Medicine (CPCVM), and each year approximately 10% of the veterinary students choose the public/corporate veterinary medicine track. The faculty of the CPCVM, and their many partners from the veterinary public practice community, teach in the veterinary curriculum and provide opportunities for students locally, nationally, and internationally during summers and the final clinical year. Graduates of the program work for government organizations, including the US Department of Agriculture, the Food and Drug Administration, and the Centers for Disease Control and Prevention, as well as in research, in industry, and for non-governmental organizations. Recent activities include securing opportunities for students, providing career counseling for graduate veterinarians interested in making a career transition, delivering continuing education, and offering a preparatory course for veterinarians sitting the board examination for the American College of Veterinary Preventive Medicine. As the VMRCVM moves forward in recognition of the changing needs of the veterinary profession, it draws on its tradition of partnership and capitalizes on the excellence of its existing program. Future plans for the CPCVM include possible expansion in the fields of public health, public policy, international veterinary medicine, organizational leadership, and the One Health initiative. Quality assurance and evaluation of the program is ongoing, with recognition that novel evaluation approaches will be useful and informative.


A multitrophic model to quantify the effects of marine viruses on microbial food webs and ecosystem processes.
Viral lysis of microbial hosts releases organic matter that can then be assimilated by nontargeted microorganisms. Quantitative estimates of virus-mediated recycling of carbon in marine waters, first established in the late 1990s, were originally extrapolated from marine host and virus densities, host carbon content and inferred viral lysis rates. Yet, these estimates did not explicitly incorporate the cascade of complex feedbacks associated with virus-mediated lysis. To evaluate the role of viruses in shaping community structure and ecosystem functioning, we extend dynamic multitrophic ecosystem models to include a virus component, specifically parameterized for processes taking place in the ocean euphotic zone. Crucially, we are able to solve this model analytically, facilitating evaluation of model behavior under many alternative parameterizations. Analyses reveal that the addition of a virus component promotes the emergence of complex communities. In addition, biomass partitioning of the emergent multitrophic community is consistent with well-established empirical norms in the surface oceans. At steady state, ecosystem fluxes can be probed to characterize the effects that viruses have when compared with putative marine surface ecosystems without viruses. The model suggests that ecosystems with viruses will have (1) increased organic matter recycling, (2) reduced transfer to higher trophic levels and (3) increased net primary productivity. These model findings support hypotheses that viruses can have significant stimulatory effects across whole-ecosystem scales. We suggest that existing efforts to predict carbon and nutrient cycling without considering virus effects are likely to miss essential features of marine food webs that regulate global biogeochemical cycles.


A Barrier for Further Approximating Sorting by Transpositions.
The transposition distance problem is a classical problem in genome rearrangements, which seeks to determine the minimum number of transpositions needed to transform a linear chromosome into another represented by the permutations π and σ, respectively. This article focuses on the equivalent problem of sorting by transpositions (SBT), where σ is the identity permutation ι. Specifically, we investigate palisades, a family of permutations that are "hard" to sort, as they require numerous transpositions above the celebrated lower bound devised by Bafna and Pevzner. By determining the transposition distance of palisades, we were able to provide the exact transposition diameter for 3-permutations (TD3), a special subset of the symmetric group Sn, essential for the study of approximate solutions for SBT using the simplification technique. The exact value for TD3 has remained unknown since Elias and Hartman showed an upper bound for it. Another consequence of determining the transposition distance of palisades is that, using as lower bound the one by Bafna and Pevzner, it is impossible to guarantee approximation ratios lower than 1.375 when approximating SBT. This finding has significant implications for the study of SBT, as this problem has been the subject of intense research efforts for the past 25 years.


Controversies in the determination of energy requirements.
To avoid any negative outcomes associated with under- or overfeeding it is essential to estimate nutrient requirements before commencing nutrition support. The energy requirements of an individual vary with current and past nutritional status, clinical condition, physical activity and the goals and likely duration of treatment. The evidence-base for prediction methods in current use, however, is poor and the equations are thus open to misinterpretation. In addition, most methods require an accurate measurement of current weight, which is problematic in some clinical situations. The estimation of energy requirements is so challenging in some conditions, e.g. critical illness, obesity and liver disease, that it is recommended that expenditure be measured on an individual basis by indirect calorimetry. Not only is this technique relatively expensive, but in the clinical setting there are several obstacles that may complicate, and thus affect the accuracy of, any such measurements. A review of relevant disease-specific literature may assist in the determination of energy requirements for some patient groups, but the energy requirements for a number of clinical conditions have yet to be established. Regardless of the method used, estimated energy requirements should be interpreted with care and only used as a starting point. Practitioners should regularly review the patient and reassess requirements to take account of any major changes in clinical condition, nutritional status, activity level and goals of treatment. There is a need for large randomised controlled trials that compare the effects of different levels of feeding on clinical outcomes in different disease states and care settings.


Failure to demonstrate short-cutting in a replication and extension of Tolman et al.'s spatial learning experiment with humans.
Successful demonstrations of novel short-cut taking by animals, including humans, are open to interpretation in terms of learning that is not necessarily spatial. A classic example is that of Tolman, Ritchie, and Kalish (1946) who allowed rats to repeat a sequence of turns through the corridors of a maze to locate a food reward. When the entrance to the corridors was subsequently blocked and alternative corridors were made available, rats successfully selected the corridor leading most directly to the food location. However, the presence of a distinctive light above the goal, in both the training and testing phases, means that approach to the light as a beacon could have been the source of successful short-cutting. We report a replication of the experimental design of Tolman et al. with human participants who explored geometrically equivalent virtual environments. An experimental group, who followed the original procedure in the absence of any distinctive cues proximal to the goal, did not select the corridor which led most directly to the goal. A control group, who experienced a light above the goal during training and testing, were more likely to select a corridor which led in the direction of the goal. A second control group experienced the light above the goal during training, but in the test the location of this cue was shifted by 90° with respect to the start point of exploration. This latter group responded unsystematically in the test, neither selecting a corridor leading to the original goal location, nor one leading directly to the relocated light cue. The results do not support the hypothesis that travelling a multi-path route automatically leads to an integrated cognitive representation of that route. The data offer support for the importance of local cues which can serve as beacons to indicate the location of a goal.


Intermittent Use of Portable NIV Increases Exercise Tolerance in COPD: A Randomised, Cross-Over Trial.
During exercise, non-invasive ventilation (NIV) prolongs endurance in chronic obstructive pulmonary disease (COPD), but routine use is impractical. The VitaBreath device provides portable NIV (pNIV); however, it can only be used during recovery. We assessed the effect of pNIV compared to pursed lip breathing (PLB) on exercise tolerance. Twenty-four COPD patients were randomised to a high-intensity (HI: 2-min at 80% peak work rate (WRpeak) alternated with 2-min recovery; n = 13), or a moderate-intensity (MOD: 6-min at 60% WRpeak alternated with 2-min recovery; n = 11) protocol, and within these groups two tests were performed using pNIV and PLB during recovery in balanced order. Upon completion, patients were provided with pNIV; use over 12 weeks was assessed. Compared to PLB, pNIV increased exercise tolerance (HI: by 5.2 ± 6.0 min; MOD: by 5.8 ± 6.7 min) (p < 0.05). With pNIV, mean inspiratory capacity increased and breathlessness decreased by clinically meaningful margins during recovery compared to the end of exercise (HI: by 140 ± 110 mL and 1.2 ± 1.7; MOD: by 170 ± 80 mL and 1.0 ± 0.7). At 12 weeks, patients reported that pNIV reduced anxiety (median: 7.5/10 versus 4/10, p = 0.001) and recovery time from breathlessness (17/24 patients; p = 0.002); 23/24 used the device at least weekly. pNIV increased exercise tolerance by reducing dynamic hyperinflation and breathlessness in COPD patients.


Nobiletin and Xanthohumol Sensitize Colorectal Cancer Stem Cells to Standard Chemotherapy.
Colorectal cancer (CRC) mortality is mainly caused by patient refractoriness to common anti-cancer therapies and consequent metastasis formation. Besides, the notorious toxic side effects of chemotherapy are a concurrent obstacle to be tackled. Thus, new treatment approaches are needed to effectively improve patient outcomes. Compelling evidence demonstrated that cancer stem cells (CSCs) are responsible for treatment failure and relapse. New natural treatment approaches showed capabilities to selectively target the CSC subpopulation by rendering them targetable by standard cytotoxic compounds. Herein we show the anti-cancer properties of the polymethoxyflavones and prenylflavonoids extracted from Citrus sinensis and Humulus lupulus, respectively. The natural biofunctional fractions, singularly and in combination, reduced the cell viability of CRC stem cells (CR-CSCs) and synergized with 5-fluorouracil and oxaliplatin (FOX) chemotherapy. These phenomena were accompanied by a reduced S and G2/M phase of the cell cycle and upregulation of cell death-related genes. Notably, both phytoextracts in combination with FOX thwarted stemness features in CR-CSCs as demonstrated by the impaired clonogenic potential and decreased Wnt pathway activation. Extracts lowered the expression of CD44v6 and affected the expansion of metastatic CR-CSCs in patients refractory to chemotherapy. Together, this study highlights the importance of polymethoxyflavones and prenylflavonoids as natural remedies to aid oncological therapies.


A case of anisakiasis invading the stomach and the colon at the same time after eating anchovies.
Anisakiasis of the gastrointestinal tract is caused by the ingestion of raw fish or uncooked food infested with Anisakis larvae. A large number of cases of gastric anisakiasis have been reported in countries where the eating of raw fish is customary. However, there have been few reports of anisakiasis of the colon confirmed by colonoscopy and also very few reports of endoscopic ultrasonographic findings of anisakiasis. A 47-year-old man had epigastric pain with nausea after eating raw anchovies. Endoscopy found a living tubular structure penetrating into the lesser curvature of the stomach and the midtranseverse colon area. It was withdrawn with biopsy forceps. We report a case of anisakiasis simultaneously invading the stomach and the colon confirmed by endosopic utrasonographic findings and biopsy findings.


Phosphoserine aminotransferase 1 is associated to poor outcome on tamoxifen therapy in recurrent breast cancer.
In a previous study, we detected a significant association between phosphoserine aminotransferase 1 (PSAT1) hyper-methylation and mRNA levels to outcome to tamoxifen treatment in recurrent disease. We here aimed to study the association of PSAT1 protein levels to outcome upon tamoxifen treatment and to obtain more insight in its role in tamoxifen resistance. A cohort of ER positive, hormonal therapy naïve primary breast carcinomas was immunohistochemically (IHC) stained for PSAT1. Staining was analyzed for association with patient's time to progression (TTP) and overall response on first-line tamoxifen for recurrent disease. PSAT1 mRNA levels were also assessed by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR; n = 161) and Affymetrix GeneChip (n = 155). Association of PSAT1 to biological pathways on tamoxifen outcome were assessed by global test. PSAT1 protein and mRNA levels were significantly associated to poor outcome to tamoxifen treatment. When comparing PSAT1 protein and mRNA levels, IHC and RT-qPCR data showed a significant association. Global test results showed that cytokine and JAK-STAT signaling were associated to PSAT1 expression. We hereby report that PSAT1 protein and mRNA levels measured in ER positive primary tumors are associated with poor clinical outcome to tamoxifen.


Right ventricular recovery during follow-up is associated with improved survival in patients with chronic heart failure with reduced ejection fraction.
A compromised tricuspid annular plane systolic excursion (TAPSE) is associated with worse survival in patients with chronic heart failure with reduced ejection fraction (HFrEF). However, it is not known whether a reversible abnormal TAPSE at follow-up predicts survival. Our aim was to evaluate whether a reversible abnormal TAPSE is associated with a better survival in patients with chronic HFrEF. A complete echocardiography was performed in 706 patients with chronic HFrEF (LVEF ≤45%) at baseline and after 6 ± 3 months. Right ventricular (RV) systolic function was evaluated using TAPSE. The study endpoint was all-cause mortality. At baseline, TAPSE was severely reduced (≤14 mm) in 89 (13%) patients, and slightly reduced (>14 but <18 mm) in 157 (22%) patients. During a median follow-up of 40 months, 152 patients reached the endpoint. The event rate (per 100 patients/year) was lower in patients with persistently normal TAPSE (≥18 mm, n = 393) [3.3%, 95% confidence interval (CI) 2.5-4.3], and in those with reversible TAPSE (n = 120) (4.6%, 95% CI 3.1-7.0), compared with patients with worsening TAPSE (n = 90) (11.9%, 95% CI 8.7-16.3), and those with persistently reduced TAPSE (n = 103) (12.6%, 95% CI 9.3-17.1; log-rank 69.4, P < 0.0001). A reversible abnormal TAPSE was associated with improved survival at multivariable Cox regression analysis (hazard ratio 0.48, 95% CI 0.29-0.79, P = 0.004). Patients with chronic HFrEF who have abnormal TAPSE at baseline but reverse their dysfunction during follow-up have better survival than patients with either worsened TAPSE or persistently abnormal TAPSE, and similar to that of patients with persistently normal TAPSE.


[The interaction of impulses evoked by stimuli of different modality in neurons of the parietal association cortex].
Interaction of visual, auditory and electro-dermal signals in neurons of the parietal associative cortex was investigated in acute experiments on cats anesthetized by chloralose and nembutal. Two types of the interaction were found, one of which was characterized by inhibition or inhibition followed by facilitation of the response to testing stimuli, and the other by facilitation or facilitation followed by inhibition of background impulses. The interaction between signals of different modality is shown to depend on the properties of the neuron. Interaction ability in polysensory neurons was evidently higher than in bi- and monosensory ones.


Th-1 cytotoxic cell-mediated response predominates in the tracheal mucosa following Mycoplasma synoviae infection of MS-H-vaccinated chickens.
Mycoplasma synoviae is a pathogen of poultry that causes upper respiratory tract disease. MS-H is a live attenuated temperature-sensitive vaccine that effectively control M. synoviae infection in chickens. However, the mechanisms underpinning protection have not been described previously. In this study, specific-pathogen-free chickens were vaccinated at 3 weeks of age with MS-H vaccine and challenged with field strain M. synoviae 94011/v-18d at 6 weeks of age. Tracheal mucosal inflammation was characterised by the assessment of thickness, histopathological lesions, cellular infiltrates and cytokine transcription. Tracheal lesion scores of unvaccinated-challenged (-V+C) birds were higher than that of vaccinated-challenged (+V+C) birds. +V+C birds displayed early upregulation of IL-4, consistent with a Th-2-skewed response, followed by a later increase in IFN-γ transcription, indicating transition to a Th-1-skewed response. -V+C birds displayed a concurrent early Th-2 and Th-17 response characterised by increase expression of IL-4 and IL-17A respectively, and late T regulatory response characterised by increased IL-10 transcription. +V+C chickens had more cytotoxic T cells (CD8+ T cells) at 7- and 21 days post-challenge (dpc), while -V+C chickens had higher numbers of infiltrating CD4+CD25+ at 7 and 21 dpc. Overall, these observations suggest that the immune response in +V+C chickens had an inflammation characterised by an early Th-2 skewed response followed closely by a Th-1 response and infiltration of cytotoxic T cells, while the response in -V+C chickens was an early Th-2/Th-17-skewed response closely followed by a T regulatory response.


SHP-1 in T cells limits the production of CD8 effector cells without impacting the formation of long-lived central memory cells.
During responses against viruses and malignancies, naive CD8 T lymphocytes expand to form both short-lived effector cells and a population containing cells with the potential to be long-lived and participate in memory responses (memory precursor effector cells). The strength of antigenic, costimulatory, and cytokine signals during responses impacts the magnitude and type of CD8 populations formed. In vitro studies have revealed that the tyrosine phosphatase Src homology region 2 domain-containing phosphatase-1 (SHP-1) regulates signal transduction from receptors on T cells including the TCR, helping set the activation threshold, and therefore may shape responses of mature CD8 T cells in vivo. Analysis of CD8 T cells from motheaten mice, which are globally deficient in SHP-1, proved problematic due to cell-extrinsic effects of SHP-1 deficiency in non-T cells on CD8 T cells. Therefore, a conditional knockout of SHP-1 in mature single-positive T cells was developed to analyze cell-intrinsic consequences of complete and partial SHP-1 deficiency on CD8 T cell responses to acute viral infection. The results demonstrated that SHP-1 has disparate effects on subpopulations of responding cells, limiting the magnitude and quality of primary and secondary responses by reducing the number of short-lived effector cells generated without affecting the size of the memory precursor effector cell pool that leads to formation of long-term memory.


General method for production and selection of infectious vaccinia virus recombinants expressing foreign genes.
The production and selection of infectious vaccinia virus recombinants expressing foreign genes was facilitated by the construction of plasmid vectors. These vectors contain all or part of the vaccinia virus thymidine kinase (TK) gene interrupted by multiple unique restriction endonuclease sites placed adjacent to the TK promoter or another promoter translocated within the TK gene. The insertion of a continuous coding sequence for a foreign protein at one of the unique restriction endonuclease sites juxtaposes the transcriptional start site of a vaccinia promoter and the translational start site of a foreign gene. After transfection of vaccinia virus-infected cells with such plasmids, homologous recombination occurs between the vaccinia virus sequences flanking the chimeric gene and the same sequences within the virus genome. Recombinants formed in this manner have the chimeric gene inserted within the body of the vaccinia virus TK gene under control of a vaccinia virus promoter. Since recombinants have an interrupted TK gene, they are selected on the basis of their TK- phenotype and then checked for the presence and expression of the foreign gene. Infectious recombinant viruses expressing the procaryotic enzyme chloramphenicol acetyltransferase were constructed to optimize the system. The absence of chloramphenicol acetyltransferase activity in uninfected cells or in cells infected with wild-type vaccinia virus and the availability of a sensitive and quantitative enzyme assay allowed an estimation of the relative strengths of various promoter constructs. The expression of chloramphenicol acetyltransferase was detected within 1 h after infection of cells with recombinant virus, reflecting the early nature of the promoters used.


The J1 adolescent health check-up: analysis of data from the German KiGGS survey.
We analyzed data from the Robert Koch Institute's KiGGS survey regarding the J1 adolescent health check-up in order to determine what information this check-up provides. Descriptive statistical analysis of J1 participation with respect to social, demographic, medical and psychological factors, with logistic regression analysis of the risk associated with non-participation. 32.9% of all adolescents in Germany aged 14 to 17 had a J1 check-up. Thus, the J1 participation rate has remained low since the introduction of the J1 in Germany. The main conditions that were more commonly found in adolescents who had a J1 check-up were thyroid disorders (4.1% vs. 2.9%), and scoliosis (14.8% vs. 10.5%). Adolescents were only half as likely to have a J1 check-up if they were under the care of a general practitioner, rather than a pediatrician (odds ratio [OR] 0.46, 95% confidence interval [CI] 0.36-0.60). Foreign adolescents were only half as likely to have a J1 check-up as German ones (OR 0.51, 95% CI 0.31-0.84). There is compelling evidence that scoliosis and thyroid disorders, in particular, are underdiagnosed if a J1 check-up is not performed. Thus, elevating the J1 participation rate should be a priority. If a J1-check up were performed in the nearly two-thirds of all adolescents who currently do not undergo one, many latent health problems could be recognized and treated in timely fashion.


The cloning and characterization of a maternally expressed novel zinc finger nuclear phosphoprotein (xnf7) in Xenopus laevis.
We report the cloning of a cDNA (xnf7) coding for a maternally expressed Xenopus protein that becomes highly enriched in nuclei of the central nervous system during later development and in nuclei of adult brain. The protein also shows stage-specific nuclear/cytoplasmic partitioning and phosphorylation that may be related to its function. In addition, it binds to double-stranded DNA in vitro. The conceptual protein produced by the xnf7 clone contains several acidic domains, a novel zinc finger domain, three putative p34cdc2 protein kinase phosphorylation sites, and a bipartite basic nuclear localization signal. The xnf7 mRNA was detected as a maternal transcript that decreased in abundance during development through the gastrula stage. It was reexpressed at the neural stage in mesoderm and neural tissues, and its reexpression was not dependent upon the normal juxtaposition of the mesoderm and ectoderm that occurs during neural induction as demonstrated by high titer in exogastrulae. In situ hybridization showed enrichment of the mRNA in the neural tube and a small amount in the mesoderm at the late neurula stage. Xnf7 is normally phosphorylated during oocyte maturation. The bacterially expressed xnf7 protein was phosphorylated in vitro by purified maturation-promoting factor at a threonine in a small N-terminal domain containing one of the p34cdc2 protein kinase phosphorylation sites, but not by several other protein kinases. The structural domains present in the protein and its localization in nuclei suggest that the xnf7 gene product performs an important nuclear function during early development, perhaps as a transcription factor or a structural component of chromatin.


Grammatical Inference: Introduction and Survey-Part II.
Inference of high-dimensional grammars is discussed. Specifically, techniques for inferring tree grammars are briefly presented. The problem of inferring a stochastic grammar to model the behavior of an information source is also introduced and techniques for carrying out the inference process are presented for a class of stochastic finite-state and context-free grammars. The possible practical application of these methods is illustrated by examples.


The Hog1 mitogen-activated protein kinase mediates a hypoxic response in Saccharomyces cerevisiae.
We have studied hypoxic induction of transcription by studying the seripauperin (PAU) genes of Saccharomyces cerevisiae. Previous studies showed that PAU induction requires the depletion of heme and is dependent upon the transcription factor Upc2. We have now identified additional factors required for PAU induction during hypoxia, including Hog1, a mitogen-activated protein kinase (MAPK) whose signaling pathway originates at the membrane. Our results have led to a model in which heme and ergosterol depletion alters membrane fluidity, thereby activating Hog1 for hypoxic induction. Hypoxic activation of Hog1 is distinct from its previously characterized response to osmotic stress, as the two conditions cause different transcriptional consequences. Furthermore, Hog1-dependent hypoxic activation is independent of the S. cerevisiae general stress response. In addition to Hog1, specific components of the SAGA coactivator complex, including Spt20 and Sgf73, are also required for PAU induction. Interestingly, the mammalian ortholog of Spt20, p38IP, has been previously shown to interact with the mammalian ortholog of Hog1, p38. Taken together, our results have uncovered a previously unknown hypoxic-response pathway that may be conserved throughout eukaryotes.


Comparison of foldback sequences of herpes simplex virus types 1 and 2 DNA.
The DNAs of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) were separately denatured and allowed to renature briefly. The intrastand foldback structures that resulted from base pairing of inverted repeated sequences on otherwise single-stranded (ss) DNA were visualized in the electron microscope. The two genomes were found to contain similar size classes of small duplex stem DNA sequences. However, HSV-2 DNA appeared to possess an additional, larger size class of foldback structures not found on HSV-1 DNA. Both HSV DNAs were found to contain stem-plus-loop structures; the larger stem-plus-loop structures of the two genomes had similar stem lengths but dissimilar loop lengths. Thus, a comparison of the genomes of HSV-1 and HSV-2 showed that they possessed similar size classes of foldback sequences.


Structures and Chromogenic Ion-Pair Recognition of a Catechol-Functionalized 1,8-Anthraquinone Macrocycle in Dimethyl Sulfoxide.
A lariat anthraquinone macrocycle functionalized with catechol (H2L) was synthesized via the Mannich reaction. The Mannich base H2L can be partially decomposed into L1·3H2O and HL1·NO3·2H2O in the presence of tetrabutylammonium hydroxide/Al(NO3)3·9H2O in dimethyl sulfoxide (DMSO). Free L1·3H2O is essentially coplanar, while protonated HL1·NO3·2H2O is highly distorted. Dark-green FeCl3·H2L·2H2O powder and Fe2(HL)2Cl4 crystal can be isolated from ethanol (C2H5OH) in high/low H2L concentration. Anthraquinone in H2L is essentially coplanar but distorted in Fe2(HL)2Cl4. The Fe(III) ion in Fe2(HL)2Cl4 adopts a less common five-coordination with three catecholate O and two Cl atoms in the dimer. The distortion of inbound C═O is much higher than that of outbound C═O in anthraquinone in all of these compounds. H2L responds to chlorides of Li+, Na+, K+, Cs+, Mg2+, Ca2+, Sr2+, Ba2+, Fe3+, Cu2+, Zn2+, and Al3+ in a DMSO solution, which can be observed by differential pulse voltammetry, UV-vis, and 1H NMR. All of these metal ions shift Ep of anthraquinone to positive, especially the second reduction peak of anthraquinone. Fe3+, Zn2+, and Al3+ change the reduction of catechol fundamentally. H2L (0.50 mM) shows a chromogenic response to FeCl3 and Fe(NO3)3 to form uncommon 2:1 and 3:2 (H2L/Fe) complexes, both peaking at 748 nm in DMSO. In the presence of 2 equiv of sodium hydroxide (NaOH), the 748 nm absorbance shifts to 777 nm, identical with Fe2(HL)2Cl4 in DMSO. Different from the fast reaction between H2L and FeCl3, Fe(NO3)3 reacts with H2L rather slowly in DMSO. Catechol can coordinate to FeCl3 without any deprotonation in C2H5OH and DMSO. H2L also shows a chromogenic response to fluorides and hydroxides, which peak at 670 and 684 nm, respectively, in DMSO. The binding ratio between H2L and F-/OH- is 1:2. In a higher concentration of hydroxides, a 684 nm greenish-blue 1:2 complex forms immediately, which gradually transforms to a red complex and peaks at ∼530 nm in minutes at room temperature. No color change can be observed in an C2H5OH solution in the presence of OH-.


Comparative analysis of prototype two-component systems with either bifunctional or monofunctional sensors: differences in molecular structure and physiological function.
Signal transduction by a traditional two-component system involves a sensor protein that recognizes a physiological signal, autophosphorylates and transfers its phosphate, and a response regulator protein that receives the phosphate, alters its affinity toward specific target proteins or DNA sequences and causes change in metabolic activity or gene expression. In some cases the sensor protein, when unphosphorylated, has a positive effect upon the rate of dephosphorylation of the regulator protein (bifunctional sensor), whereas in other cases it has no such effect (monofunctional sensor). In this work we identify structural and functional differences between these two designs. In the first part of the paper we use sequence data for two-component systems from several organisms and homology modelling techniques to determine structural features for response regulators and for sensors. Our results indicate that each type of reference sensor (bifunctional and monofunctional) has a distinctive structural feature, which we use to make predictions regarding the functionality of other sensors. In the second part of the paper we use mathematical models to analyse and compare the physiological function of systems that differ in the type of sensor and are otherwise equivalent. Our results show that a bifunctional sensor is better than a monofunctional sensor both at amplifying changes in the phosphorylation level of the regulator caused by signals from the sensor and at attenuating changes caused by signals from small phosphodonors. Cross-talk to or from other two-component systems is better suppressed if the transmitting sensor is monofunctional, which is the more appropriate design when such cross-talk represents pathological noise. Cross-talk to or from other two-component systems is better amplified if the transmitting sensor is bifunctional, which is the more appropriate design when such cross-talk represents a physiological signal. These results provide a functional rationale for the selection of each design that is consistent with available experimental evidence for several two-component systems.


Homomeric interaction of AtVSR1 is essential for its function as a vacuolar sorting receptor.
Vacuolar sorting receptors, BP80/VSRs, play a critical role in vacuolar trafficking of soluble proteins in plant cells. However, the mechanism of action of BP80 is not well understood. Here, we investigate the action mechanism of AtVSR1, a member of BP80 proteins in Arabidopsis (Arabidopsis thaliana), in vacuolar trafficking. AtVSR1 exists as multiple forms, including a high molecular mass homomeric complex in vivo. Both the transmembrane and carboxyl-terminal cytoplasmic domains of AtVSR1 are necessary for the homomeric interaction. The carboxyl-terminal cytoplasmic domain contains specific sequence information, whereas the transmembrane domain has a structural role in the homomeric interaction. In protoplasts, an AtVSR1 mutant, C2A, that contained alanine substitution of the region involved in the homomeric interaction, was defective in trafficking to the prevacuolar compartment and localized primarily to the trans-Golgi network. In addition, overexpression of C2A, but not wild-type AtVSR1, inhibited trafficking of soluble proteins to the vacuole and caused their secretion into the medium. Furthermore, C2A:hemagglutinin in transgenic plants interfered with the homomeric interaction of endogenous AtVSR1 and inhibited vacuolar trafficking of sporamin:green fluorescent protein. These data suggest that homomeric interaction of AtVSR1 is critical for its function as a vacuolar sorting receptor.


Treatment-related improvement in physical function varies with duration of rheumatoid arthritis: a pooled analysis of clinical trial results.
Physical function in rheumatoid arthritis (RA) has reversible and irreversible components, and is typically assessed by the Health Assessment Questionnaire Disability Index (HAQ). Since irreversible components are expected to increase with longer duration of RA and reduce the ability for improvement in physical function, we analysed responsiveness of HAQ scores in patient populations with differing RA durations in randomised controlled trials (RCTs). Data from all RCTs published between 1980 and 2005 that reported changes from baseline in HAQ at 6 and/or 12 months were analysed. Treatments were grouped as "biologics", or "traditional" disease modifying antirheumatic drugs (DMARDs), and "placebo". We computed effect sizes of HAQ in each trial, and contrasted the association between these effects and duration of RA among treatment groups using regression models. We identified 42 RCTs with complete data for the statistical models. The models indicate that discrimination of functional improvement between active drug groups and placebo is reduced in patients with a longer duration of RA (p = 0.02 for the change in discrimination over time). The placebo-adjusted HAQ responses decreased on average by 0.37 per year of RA duration. Responsiveness in HAQ scores is inversely associated with mean disease duration in RA. This impacts assessment of physical function, a key outcome measure in RCTs and practice, and impacts the ability to discriminate active treatment from placebo.


Sonochemical synthesis of lanthanum ferrite nanoparticle-decorated carbon nanotubes for simultaneous electrochemical determination of acetaminophen and dopamine.
A new nanocomposite consisting of lanthanum ferrite nanoparticles (LaFeO3 NPs) integrated with carbon nanotubes (CNTs) was fabricated via facile sonochemical approach. The engineered nanocomposite was applied to simultaneously determine acetaminophen (ACP) and dopamine (DA) in a binary mixture. The LaFeO3 NPs@CNT probe possesses several advantages such as superior conductivity, large surface area, and more active sites, improving its electrocatalytic activity towards ACP and DA. Under optimized conditions, the anodic peak currents (Ipa) linearly increased with increasing concentration of ACP and DA in the range 0.069-210 µM and 0.15-210 µM, respectively. The sensitivity of LaFeO3 NPs@CNTs/glassy carbon electrode (GCE) for detecting ACP and DA is 7.456 and 5.980 μA·μM-1·cm-2, respectively. The detection limits (S/N = 3) for ACP and DA are 0.02 μM and 0.05 μM, respectively. Advantages of LaFeO3 NPs@CNTs/GCE for the detection of ACP and DA include wide linear ranges, low-detection limits, good selectivity, and long-term stability. The as-fabricated electrode was applied to determine ACP and DA in pharmaceutical formulations and human serum samples with recoveries ranging from 97.7 to 103.3% and an RSD that did not exceed 3.7%, confirming the suitability of the proposed sensor for the determination of ACP and DA in real samples. This study not only presents promising opportunities for enhancing the sensitivity and stability of electrochemical sensors used in the detection of bioanalytes but also significantly contributes to the progress of unique and comprehensive biochemical detection methodologies.


Hormonal regulation of inner medullary collecting duct sodium transport.
The inner medullary collecting duct (IMCD) is the final arbiter of renal Na+ excretion, and Na+ transport in this segment is controlled by a wide variety of hormones and renal autacoids. This review examines the mechanisms of IMCD Na+ transport and its regulation using results obtained from micropuncture and microcatheterization studies in the intact animal, as well as data from isolated perfused tubules, freshly prepared cell suspensions, and cultured IMCD cells. Where appropriate, results from closely related tissues such as the cortical collecting duct and model urinary epithelia are examined. Na+ reabsorption in this segment occurs predominantly via apical amiloride-sensitive Na+ channels and basolateral Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase). Although there is some evidence for the activities of other transporters such as Na(+)-K(+)-2Cl- and Na-Cl cotransporters and Na+/H+ exchanger, their role in Na+ homeostasis remains undefined. Mineralocorticoids augment the activities of both apical Na+ channels and basolateral Na(+)-K(+)-ATPase by a variety of complex mechanisms. Prostaglandin E2 inhibits Na(+)-K(+)-ATPase and appears to mediate the actions of several peptide hormones, including endothelin, interleukin-1, and atrial natriuretic peptide [ANP-(31-67)]. Several peptides in the ANP family [ANP-(99-126), urodilatin, and brain natriuretic peptide] bind to guanylate cyclase-linked receptors, leading to inhibition of apical Na+ channel function. These mechanisms of regulation of IMCD Na+ transport likely play important roles in total body Na+ balance in health and disease.


Phytomelatonin: assisting plants to survive and thrive.
This review summarizes the advances that have been made in terms of the identified functions of melatonin in plants. Melatonin is an endogenously-produced molecule in all plant species that have been investigated. Its concentration in plant organs varies in different tissues, e.g., roots versus leaves, and with their developmental stage. As in animals, the pathway of melatonin synthesis in plants utilizes tryptophan as an essential precursor molecule. Melatonin synthesis is inducible in plants when they are exposed to abiotic stresses (extremes of temperature, toxins, increased soil salinity, drought, etc.) as well as to biotic stresses (fungal infection). Melatonin aids plants in terms of root growth, leaf morphology, chlorophyll preservation and fruit development. There is also evidence that exogenously-applied melatonin improves seed germination, plant growth and crop yield and its application to plant products post-harvest shows that melatonin advances fruit ripening and may improve food quality. Since melatonin was only discovered in plants two decades ago, there is still a great deal to learn about the functional significance of melatonin in plants. It is the hope of the authors that the current review will serve as a stimulus for scientists to join the endeavor of clarifying the function of this phylogenetically-ancient molecule in plants and particularly in reference to the mechanisms by which melatonin mediates its multiple actions.


Electrochemically Synthesized Poly(3-hexylthiophene) Nanowires as Photosensitive Neuronal Interfaces.
Poly(3-hexylthiophene) (P3HT) is a hole-conducting polymer that has been intensively used to develop organic optoelectronic devices (e.g., organic solar cells). Recently, P3HT films and nanoparticles have also been used to restore the photosensitivity of retinal neurons. The template-assisted electrochemical synthesis of polymer nanowires advantageously combines polymerization and polymer nanostructuring into one, relatively simple, procedure. However, obtaining P3HT nanowires through this procedure was rarely investigated. Therefore, this study aimed to investigate the template-assisted electrochemical synthesis of P3HT nanowires doped with tetrabutylammonium hexafluorophosphate (TBAHFP) and their biocompatibility with primary neurons. We show that template-assisted electrochemical synthesis can relatively easily turn 3-hexylthiophene (3HT) into longer (e.g., 17 ± 3 µm) or shorter (e.g., 1.5 ± 0.4 µm) P3HT nanowires with an average diameter of 196 ± 55 nm (determined by the used template). The nanowires produce measurable photocurrents following illumination. Finally, we show that primary cortical neurons can be grown onto P3HT nanowires drop-casted on a glass substrate without relevant changes in their viability and electrophysiological properties, indicating that P3HT nanowires obtained by template-assisted electrochemical synthesis represent a promising neuronal interface for photostimulation.


Identification of Plasmodium falciparum RhopH3 protein peptides that specifically bind to erythrocytes and inhibit merozoite invasion.
The identification of sequences involved in binding to erythrocytes is an important step for understanding the molecular basis of merozoite-erythrocyte interactions that take place during invasion of the Plasmodium falciparum malaria parasite into host cells. Several molecules located in the apical organelles (micronemes, rhoptry, dense granules) of the invasive-stage parasite are essential for erythrocyte recognition, invasion, and establishment of the nascent parasitophorous vacuole. Particularly, it has been demonstrated that rhoptry proteins play an important role in binding to erythrocyte surface receptors, among which is the PfRhopH3 protein, which triggers important immune responses in patients from endemic regions. It has also been reported that anti-RhopH3 antibodies inhibit in vitro invasion of erythrocytes, further supporting its direct involvement in erythrocyte invasion processes. In this study, PfRhopH3 consecutive peptides were synthesized and tested in erythrocyte binding assays for identifying those regions mediating binding to erythrocytes. Fourteen PfRhopH3 peptides presenting high specific binding activity were found, whose bindings were saturable and presented nanomolar dissociation constants. These high-activity binding peptides (HABPs) were characterized by having alpha-helical structural elements, as determined by circular dichroism, and having receptors of a possible sialic acid-dependent and/or glycoprotein-dependent nature, as evidenced in enzyme-treated erythrocyte binding assays and further corroborated by cross-linking assay results. Furthermore, these HABPs inhibited merozoite in vitro invasion of normal erythrocytes at 200 microM by up to 60% and 90%, suggesting that some RhopH3 protein regions are involved in the P. falciparum erythrocyte invasion.


[Experience with the management of fresh cruciate ligament rupture in athletes].
Since 1984 we have done over the top repair of the acutely torn anterior cruciate ligament combined with augmentation by McIntosh lateral-substitution over the top procedure with iliotibial band in view of frequent instabilities following simple reconstruction. After treatment by continuous passive motion and early weight bearing is possible. The results at review were good. This method is recommended to avoid the risk of rerupture.


Mental health professionals' perspectives on the relevance of religion and spirituality to mental health care.
A large body of evidence indicates that spiritual and religious backgrounds, beliefs, and practices (SRBBPs) are related to better psychological health. Spirituality and religion (R/S) are also important aspects of multicultural diversity. There is evidence that clients would like to talk about their spirituality, and that including it in assessment and treatment planning can be beneficial. However, the extent to which practicing mental health professionals view SRBBPs as relevant to mental health and clinical practice is unclear. A survey examining several aspects of addressing SRBBPs in clinical practice was distributed to 894 professionals across mental health disciplines, including psychiatry, psychology, social work, marriage family therapy, licensed professional counselors, certified chemical dependency counselors, and psychiatric mental health nurses. 89% of mental health professionals agreed that clinicians should receive training in R/S competencies. There were no differences between mental health disciplines in ratings of importance of such training. Younger individuals and those who identify as more spiritual were more likely to consider R/S training as important. Although 47.1% of professionals had not received much R/S training, many perceived themselves to be highly competent in R/S clinical integration practices (57.8% considered themselves able to display them very much or completely). In addition, respondents with more R/S training evaluated themselves as more proficient in R/S clinical integration. Nearly two-thirds (65.2%) of respondents reported encountering few to no barriers to engaging in R/S competent mental health care. There is a growing consensus among mental health care professionals that mental health professionals should be trained in R/S competencies. Strong agreement exists that basic R/S competencies include respect, empathy, examination of bias, and routine assessment of R/S in mental health care. Four in five of those surveyed agree that more active competencies, such as identifying and addressing religious and spiritual struggles and problems and helping clients explore and access R/S strengths and resources should be included, whereas one in five report less comfort with these competencies.


Birth weight, breast cancer and the potential mediating hormonal environment.
Previous studies have shown that woman's risk of breast cancer in later life is associated with her infants birth weights. The objective of this study was to determine if this association is independent of breast cancer risk factors, mother's own birth weight and to evaluate association between infants birth weight and hormonal environment during pregnancy. Independent association would have implications for understanding the mechanism, but also for prediction and prevention of breast cancer. Risk of breast cancer in relation to a first infant's birth weight, mother's own birth weight and breast cancer risk factors were evaluated in a prospective cohort of 410 women in the Framingham Study. Serum concentrations of estriol (E3), anti-estrogen alpha-fetoprotein (AFP), and pregnancy-associated plasma protein-A (PAPP-A) were measured in 23,824 pregnant women from a separate prospective cohort, the FASTER trial. During follow-up (median, 14 years) 31 women (7.6%) were diagnosed with breast cancer. Women with large birth weight infants (in the top quintile) had a higher breast cancer risk compared to other women (hazard ratio (HR), 2.5; 95% confidence interval (CI), 1.2-5.2; P = 0.012). The finding was not affected by adjustment for birth weight of the mother and traditional breast cancer risk factors (adjusted HR, 2.5; 95% CI, 1.2-5.6; P = 0.021). An infant's birth weight had a strong positive relationship with the mother's serum E3/AFP ratio and PAPP-A concentration during pregnancy. Adjustment for breast cancer risk factors did not have a material effect on these relationships. Giving birth to an infant with high birth weight was associated with increased breast cancer risk in later life, independently of mother's own birth weight and breast cancer risk factors and was also associated with a hormonal environment during pregnancy favoring future breast cancer development and progression.


En bloc excision and autogenous fibular reconstruction for aggressive giant cell tumor of distal radius: a report of 12 cases and review of literature.
Giant cell tumor (GCT) of distal radius follows a comparatively aggressive behaviour. Wide excision is the management of choice, but this creates a defect at the distal end of radius. The preffered modalities for reconstruction of such a defect include vascularized/non-vascularized bone graft, osteoarticular allografts and custom-made prosthesis. We here present our experience with wide resection and non-vascularised autogenous fibula grafting for GCT of distal radius. Twelve patients with a mean age of 34.7 years (21-43 years) with Campanacci Grade II/III GCT of distal radius were managed with wide excision of tumor and reconstruction with ipsilateral nonvascularised fibula, fixed with small fragment plate to the remnant of the radius. Primary autogenous iliac crest grafting was done at the fibuloradial junction in all the patients. Mean follow up period was 5.8 years (8.2-3.7 years). Average time for union at fibuloradial junction was 33 weeks (14-69 weeks). Mean grip strength of involved side was 71% (42-86%). The average range of movements were 52° forearm supination, 37° forearm pronation, 42° of wrist palmerflexion and 31° of wrist dorsiflexion with combined movements of 162°. Overall revised musculoskeletal tumor society (MSTS) score averaged 91.38% (76.67-93.33%) with five excellent, four good and three satisfactory results. There were no cases with graft related complications or deep infections, 3 cases with wrist subluxation, 2 cases with non union (which subsequently united with bone grafting) and 1 case of tumor recurrence. Although complication rate is high, autogenous non-vascularised fibular autograft reconstruction of distal radius can be considered as a reasonable option after en bloc excision of Grade II/III GCT.


Diuresis of cirrhotic ascites increases its opsonic activity and may help prevent spontaneous bacterial peritonitis.
Serial ascitic fluid samples were obtained during diuresis in seven patients with portal hypertension-related ascites. The samples were tested for concentrations of total protein, CH100, C3 and C4 as well as for in vitro opsonic activity. These parameters were all found to increase to a statistically significant degree when the initial specimen was compared to the final specimen: total protein = 1.5 vs. 2.7 gm per dl; CH100 = 9.3 vs. 20.2 units per ml; C3 = 13.4 vs. 23.8 mg per dl; C4 = 1.9 vs. 3.6 mg per dl, and opsonic activity = 0.8 vs. 1.9 log kill. This increased opsonic activity resulted in a greater than 10-fold increase in bacterial killing. This study demonstrates that diuresis of patients with cirrhotic ascites increases the concentrations of ascitic fluid complement components and increases the opsonic activity of ascitic fluid and may help protect patients from bacterial infection of their ascites.


Kidney Transplantation in Low- to Middle-Income Countries: Outcomes and Lessons Learned from Armenia.
BACKGROUND Treatment of end-stage renal disease constitutes a heavy financial burden, especially in developing countries. Maintaining a kidney transplantation program is an extremely complex task in countries with limited resources. It often requires expertise and support from developed countries. Living donor kidney transplantations (LDKT) have been performed regularly in the Republic of Armenia since 2002. The purpose of this article is to review the history and outcomes of kidney transplantation in Armenia. MATERIAL AND METHODS A chart review was performed retrospectively on all patients who had undergone LDKT in Armenia. The key personnel involved in the development and operation of the unique kidney transplant program in the country were interviewed for a comprehensive review of the history and challenges of transplantation. RESULTS There were 172 LDKT (4 re-transplantations) performed between 2002 and 2019. The mean age of recipients was 35.9±13.4 years (range 7.1-65.7): 116 (67.4%) were male and 12 (6.9%) were children (<18 years). Seventy-four patients (43%) had peri- (n=5) and postoperative (n=69), mostly mild, surgical complications. Delayed graft function occurred in 17 (9.9%) patients, requiring hemodialysis in 16, and 6 patients stayed HD-dependant. Sixty-nine patients (40.1%) had at least 1 episode of acute rejection, with 26 (15.1%) having more than 1. Late complications were mostly infectious (n=49) or malignant processes (n=13). Follow-up studies showed that out of 172 patients, 126 had functioning grafts, 17 died with functioning grafts, 3 were lost to follow-up, and 26 lost grafts. Graft survival at 1, 3, 5, and 10 years, non-censored for death, after LDKT was 96.4% (CI 93.6-99.2), 93.7% (CI 89.9-97.5), 90.5% (CI 85.7-95.3), and 75.3% (CI 66.9-83.7), respectively. CONCLUSIONS Findings from this study suggest that a renal transplant program with acceptable outcomes can be successfully introduced in countries with limited resources.


Preparing large-aspect-ratio prolate metal nanoparticles in glass by simultaneous femtosecond multicolor irradiation.
By irradiating spherical metal nanoparticles embedded in glass with several hundred ultrashort laser pulses at peak intensities of 0.2-1.5 TWcm(2), dichroic microstructures can be written in these nanocomposite materials. The underlying mechanism is transformation of the nanoparticles to prolate shapes. Using a single wavelength, the maximum aspect ratio achievable with this process is limited by partial destruction of particles. Here we show that this limitation can be overcome by simultaneous irradiation with different wavelengths. In particular, adding a relatively weak intensity at 800 nm to the main irradiation at 532 nm increases the maximum aspect ratio of Ag nanoparticles and the resulting separation between polarized surface plasmon bands dramatically. These effects are explained by the efficiency of electric field enhancement in the vicinity of nanoparticles, which influences the directed photoionization needed for particle shape transformation.