Content words in Hebrew child-directed speech.
The goal of the study was to examine whether the 'noun-bias' phenomenon, which exists in the lexicon of Hebrew-speaking children, also exists in Hebrew child-directed speech (CDS) as well as in Hebrew adult-directed speech (ADS). In addition, we aimed to describe the use of the different classes of content words in the speech of Hebrew-speaking parents to their children at different ages compared to the speech of parents to adults (ADS). Thirty infants (age range 8:5-33 months) were divided into three stages according to age: pre-lexical, single-word, and early grammar. The ADS corpus included 18 Hebrew-speaking parents of children at the same three stages of language development as in the CDS corpus. The CDS corpus was collected from parent-child dyads during naturalistic activities at home: mealtime, bathing, and play. The ADS corpus was collected from parent-experimenter interactions including the parent watching a video and then being interviewed by the experimenter. 200 utterances of each sample were transcribed, coded for types and tokens and analyzed quantitatively and qualitatively. Results show that in CDS, when speaking to infants of all ages, parents' use of types and tokens of verbs and nouns was similar and significantly higher than their use of adjectives or adverbs. In ADS, however, verbs were the main lexical category used by Hebrew-speaking parents in both types and tokens. It seems that both the properties of the input language (e.g. the pro-drop parameter) and the interactional styles of the caregivers are important factors that may influence the high presence of verbs in Hebrew-speaking parents' ADS and CDS. The negative correlation between the widespread use of verbs in the speech of parents to their infants and the 'noun-bias' phenomenon in the Hebrew-child lexicon will be discussed in detail.


Human antibodies targeting Zika virus NS1 provide protection against disease in a mouse model.
Zika virus is a mosquito-borne flavivirus closely related to dengue virus that can cause severe disease in humans, including microcephaly in newborns and Guillain-Barré syndrome in adults. Specific treatments and vaccines for Zika virus are not currently available. Here, we isolate and characterize four monoclonal antibodies (mAbs) from an infected patient that target the non-structural protein NS1. We show that while these antibodies are non-neutralizing, NS1-specific mAbs can engage FcγR without inducing antibody dependent enhancement (ADE) of infection in vitro. Moreover, we demonstrate that mAb AA12 has protective efficacy against lethal challenges of African and Asian lineage strains of Zika virus in Stat2-/- mice. Protection is Fc-dependent, as a mutated antibody unable to activate known Fc effector functions or complement is not protective in vivo. This study highlights the importance of the ZIKV NS1 protein as a potential vaccine antigen.


Continuous Wavelet Transform, a powerful alternative to Derivative Spectrophotometry in analysis of binary and ternary mixtures: A comparative study.
A comparative study was established between two signal processing techniques showing the theoretical algorithm for each method and making a comparison between them to indicate the advantages and limitations. The methods under study are Numerical Differentiation (ND) and Continuous Wavelet Transform (CWT). These methods were studied as spectrophotometric resolution tools for simultaneous analysis of binary and ternary mixtures. To present the comparison, the two methods were applied for the resolution of Bisoprolol (BIS) and Hydrochlorothiazide (HCT) in their binary mixture and for the analysis of Amlodipine (AML), Aliskiren (ALI) and Hydrochlorothiazide (HCT) as an example for ternary mixtures. By comparing the results in laboratory prepared mixtures, it was proven that CWT technique is more efficient and advantageous in analysis of mixtures with severe overlapped spectra than ND. The CWT was applied for quantitative determination of the drugs in their pharmaceutical formulations and validated according to the ICH guidelines where accuracy, precision, repeatability and robustness were found to be within the acceptable limit.


Effective learning strategies for real-time image-guided adaptive control of multiple-source hyperthermia applicators.
This paper investigates overall theoretical requirements for reducing the times required for the iterative learning of a real-time image-guided adaptive control routine for multiple-source heat applicators, as used in hyperthermia and thermal ablative therapy for cancer. Methods for partial reconstruction of the physical system with and without model reduction to find solutions within a clinically practical timeframe were analyzed. A mathematical analysis based on the Fredholm alternative theorem (FAT) was used to compactly analyze the existence and uniqueness of the optimal heating vector under two fundamental situations: (1) noiseless partial reconstruction and (2) noisy partial reconstruction. These results were coupled with a method for further acceleration of the solution using virtual source (VS) model reduction. The matrix approximation theorem (MAT) was used to choose the optimal vectors spanning the reduced-order subspace to reduce the time for system reconstruction and to determine the associated approximation error. Numerical simulations of the adaptive control of hyperthermia using VS were also performed to test the predictions derived from the theoretical analysis. A thigh sarcoma patient model surrounded by a ten-antenna phased-array applicator was retained for this purpose. The impacts of the convective cooling from blood flow and the presence of sudden increase of perfusion in muscle and tumor were also simulated. By FAT, partial system reconstruction directly conducted in the full space of the physical variables such as phases and magnitudes of the heat sources cannot guarantee reconstructing the optimal system to determine the global optimal setting of the heat sources. A remedy for this limitation is to conduct the partial reconstruction within a reduced-order subspace spanned by the first few maximum eigenvectors of the true system matrix. By MAT, this VS subspace is the optimal one when the goal is to maximize the average tumor temperature. When more than 6 sources present, the steps required for a nonlinear learning scheme is theoretically fewer than that of a linear one, however, finite number of iterative corrections is necessary for a single learning step of a nonlinear algorithm. Thus, the actual computational workload for a nonlinear algorithm is not necessarily less than that required by a linear algorithm. Based on the analysis presented herein, obtaining a unique global optimal heating vector for a multiple-source applicator within the constraints of real-time clinical hyperthermia treatments and thermal ablative therapies appears attainable using partial reconstruction with minimum norm least-squares method with supplemental equations. One way to supplement equations is the inclusion of a method of model reduction.


Effect of Age on Clinical Outcomes in Phase 1 Trial Participants.
Most persons with cancer living in the United States are older than 65 years of age; however, in general, elderly persons are under-represented in clinical trials and outcomes data are lacking. Outcomes data were analyzed of elderly participants (≥65 years of age) enrolled in phase 1 clinical trials and the results compared with those of younger patients. All consecutive, single-center, phase 1 oncology trials initiated and completed at the H. Lee Moffitt Cancer Center & Research Institute between 1997 and 2007 were included. Patient data (including survival, response, and toxicity rates) were extracted from a cancer registry database and electronic medical records at Moffitt Cancer Center. After excluding multi-institution trials, we analyzed 39 trials for a total of 1,162 enrolled study participants, 32.7% of whom were elderly. Among patients who underwent transplantation, median survival rates were worse in those who were elderly compared with those who were younger (44.9 vs 32.9 months; P = .0037). However, in the no-transplantation setting, participants who were elderly had a median survival rate of 10.9 months (95% confidence interval [CI]: 8.9-13.1) compared with 8.8 months (95% CI: 7.9-10.3) in those who were younger (P = .15). Both groups had similar overall response rates (15.2% vs 13.1%) and similar treatment-related mortality rates (1% vs 0.9%, respectively). Adverse events occurring among the elderly and younger participants were not statistically significant. Survival, response, toxicity, and treatment-related mortality rates were not significantly different between the elderly and younger phase 1 trial participants in the no-transplantation setting. Regardless of the complex pharmacological profiles and logistical issues involved in treating the elderly population, our data imply that elderly study participants do at least as well as their younger counterparts, contributing to the justification of increasing the phase 1 trial enrollment of elderly patients.


Clinical Assessment and Etiological Evaluation of Optic Nerve Atrophy.
Optic atrophy results from the disease process that cause irreversible damage to the ganglion cells and the anterior visual pathway, but may also result from posterior visual pathway involvement. The etiology causing this condition is vast and regardless of underlying cause it carries bad visual prognosis and at times may be life threatening. The study aims to assess patients with optic nerve atrophy presenting to B.P. Koirala lions centre for ophthalmic studies and identify the underlying etiology. This is a descriptive study conducted at B.P. Koirala Lions Centre for Ophthalmic studies. All cases of optic atrophy who presented to our outpatient department from March 2016 to March 2017 were included in the study. In addition to detailed evaluation, assessment of visual acuity, color vision, contrast sensitivity and visual field were done if feasible. Other relevant investigations were conducted to establish the underlying etiological cause. A total of 62 patients were included in the study, with 35 patients having bilateral disease and 27 having unilateral disease accounting for 97 eyes with optic atrophy. The mean age of the affected was 40.63±17.36 years with male to female ratio of 1.2:1. The most common etiology for optic atrophy was traumatic neuropathy (n=16, 25.8%). Majority of eyes had pale disc (n=70, 72.2%) and the rest had temporal pallor (n=27, 27.8%). Traumatic optic neuropathy was the most common etiological cause of optic nerve atrophy.


Induction of efflux-mediated macrolide resistance in Streptococcus pneumoniae.
The antimicrobial efflux system encoded by the operon mef(E)-mel on the mobile genetic element MEGA in Streptococcus pneumoniae and other Gram-positive bacteria is inducible by macrolide antibiotics and antimicrobial peptides. Induction may affect the clinical response to the use of macrolides. We developed mef(E) reporter constructs and a disk diffusion induction and resistance assay to determine the kinetics and basis of mef(E)-mel induction. Induction occurred rapidly, with a >15-fold increase in transcription within 1 h of exposure to subinhibitory concentrations of erythromycin. A spectrum of environmental conditions, including competence and nonmacrolide antibiotics with distinct cellular targets, did not induce mef(E). Using 16 different structurally defined macrolides, induction was correlated with the amino sugar attached to C-5 of the macrolide lactone ring, not with the size (e.g., 14-, 15- or 16-member) of the ring or with the presence of the neutral sugar cladinose at C-3. Macrolides with a monosaccharide attached to C-5, known to block exit of the nascent peptide from the ribosome after the incorporation of up to eight amino acids, induced mef(E) expression. Macrolides with a C-5 disaccharide, which extends the macrolide into the ribosomal exit tunnel, disrupting peptidyl transferase activity, did not induce it. The induction of mef(E) did not require macrolide efflux, but the affinity of macrolides for the ribosome determined the availability for efflux and pneumococcal susceptibility. The induction of mef(E)-mel expression by inducing macrolides appears to be based on specific interactions of the macrolide C-5 saccharide with the ribosome that alleviate transcriptional attenuation of mef(E)-mel.


Invertebrate community response to fire and rodent activity in the Mojave and Great Basin Deserts.
Recent increases in the frequency and size of desert wildfires bring into question the impacts of fire on desert invertebrate communities. Furthermore, consumer communities can strongly impact invertebrates through predation and top-down effects on plant community assembly. We experimentally applied burn and rodent exclusion treatments in a full factorial design at sites in both the Mojave and Great Basin deserts to examine the impact that fire and rodent consumers have on invertebrate communities. Pitfall traps were used to survey invertebrates from April through September 2016 to determine changes in abundance, richness, and diversity of invertebrate communities in response to fire and rodent treatments. Generally speaking, rodent exclusion had very little effect on invertebrate abundance or ant abundance, richness or diversity. The one exception was ant abundance, which was higher in rodent access plots than in rodent exclusion plots in June 2016, but only at the Great Basin site. Fire had little effect on the abundances of invertebrate groups at either desert site, with the exception of a negative effect on flying-forager abundance at our Great Basin site. However, fire reduced ant species richness and Shannon's diversity at both desert sites. Fire did appear to indirectly affect ant community composition by altering plant community composition. Structural equation models suggest that fire increased invasive plant cover, which negatively impacted ant species richness and Shannon's diversity, a pattern that was consistent at both desert sites. These results suggest that invertebrate communities demonstrate some resilience to fire and invasions but increasing fire and spread of invasive due to invasive grass fire cycles may put increasing pressure on the stability of invertebrate communities.


Accurate Prediction of Alzheimer's Disease Progression Trajectory via a Novel Encoder-Decoder LSTM Architecture.
With an increase in life expectancy, there has been an increase in the aged population globally, and around 10% of this population suffers from Alzheimer's disease. Alzheimer's hugely impacts the quality of life and well-being of older adults and their caregivers. Thus, it is an emerging challenge to improve the early diagnosis and prognosis of the disease. Detecting hidden patterns in complex multidimensional datasets using recent advancements in machine learning provides a tremendous opportunity to meet this crucial need. In this study, using multimodal features and an individual's clinical status on one or more time points, we aimed to predict the individual's cognitive test scores, changes in Magnetic Resonance Imaging features, and the individual's diagnostic status for the next three years. We presented a novel Encoder-Decoder Long Short-Term Memory deep-learning model architecture for implementing our prediction. We applied it to data from the Alzheimer's Disease Neuroimaging Initiative, comprising longitudinal data of 1737 participants and 12,741 instances. The proposed model was found to be competent, with a validation accuracy of 0.941, a multi-class area under the curve of 0.960, and a test accuracy of 0.88 in identifying the various stages of Alzheimer's disease progression in patients with an initially cognitively normal or mild cognitive impairment which is a significant improvement over previous methods.Clinical relevance- The proposed approach can help improve diagnostic understanding of Alzheimer's Disease progression and assist in the early detection of various stages of Alzheimer's Disease based on clinical heterogeneity.


Downregulation of ARFGEF1 and CAMK2B by promoter hypermethylation in breast cancer cells.
To identify novel genes that are regulated by promoter methylation, a combinational approach involving in silico mining followed by molecular assay was performed. From the expression microarray data registered in the European bioinformatics institute (EBI), genes showing downregulation in breast cancer cells were initially screened and then selected by e-Northern analysis using the Unigene database. A series of these in silico methods identified CAMK2B and ARFGEF1 as candidates, and the two genes were revealed to be hypermethylated in breast cancer cell lines and hypomethylated in normal breast cell lines. Additionally, cancer cell lines showed downregulated expression of these genes. Furthermore, treatment of the cancer cell lines with a demethylation agent, 5-Aza-2'-deoxycytidine, recovered expression of CAMK2B and ARFGEF1, implying that hypermethyaltion silenced gene activity in cancer cells. Taken together, promoter methylations of CAMK2B and ARFGEF1 are novel epigenetic markers identified in breast cancer cell lines and can be utilized for the application to clinical cancer tissues.


A novel high throughput approach to screen for cardiac arrhythmic events following stem cell treatment.
Although stem cell therapy is promising for repairing damaged cardiac tissue and improving heart function, there are safety concerns, especially regarding the risk of arrhythmias, which can be life threatening. To address this issue, we propose to develop a novel screening system to evaluate arrhythmic risk associated with stem cell therapy using a high-throughput multielectrode array system that can measure conduction velocity and action potential duration in cardiomyocytes co-cultured with different types of stem cells, such as mesenchymal stem cells, skeletal myoblasts, and resident cardiac stem cells. We will assess the arrhythmic potential of each of these types of stem cells under normoxic and hypoxic conditions, with/without application of oxidative stress or catecholamines. We hypothesize that these methods will prove to be an effective way to screen for arrhythmic risk of cardiac stem cell therapy. Ultimately, our approach can potentially be personalized to develop a robust screening protocol in order to identify which stem cell type carries the least amount of risk for arrhythmia. This system will have great clinical benefit to improve the risk/benefit ratio of human stem cell therapy for heart disease.


Host H-2 haplotype modulates the induction of host-versus-graft disease after the induction of neonatal tolerance to H-2 alloantigens.
Mice injected at birth with semiallogeneic spleen cells develop a host-versus-graft disease (HVGD) characterized by the polyclonal activation of donor B cells by alloreactive host CD4+ T cells, the production of autoantibodies (autoAb) and the development of an inmmunocomplex-mediated glomerulonephritis. It has been demonstrated that the recognition of MHC class II, but not class I or non MHC, alloantigens triggers the development of the autoimmune syndrome (AIS). The finding of different expression patterns of Ia molecules in different mouse strains, and a closed restriction of some immune responses to particular H-2 haplotypes, prompted us to analyze whether variations in the expressed MHC class II molecules modify the HVGD. First, newborn BALB/c mice received spleen cells from F1 hybrid mice obtained by mating BALB/c mice with several mouse strains differing in the H-2 haplotype. Second, spleen cells from different F1 mice were neonatally injected in mice of both parental strains. All groups of BALB/c mice injected with different combinations of F1 mice showed an HVGD with a very similar serological course. However, in some instances, duration was different when comparing both parental strains injected with spleen cells from the mutual F1 hybrids. These results suggest that host MHC, but not donor MHC haplotype may modulate the AIS associated with the induction of neonatal tolerance.


Evaluation of recombinant Brachyspira pilosicoli oligopeptide-binding proteins as vaccine candidates in a mouse model of intestinal spirochaetosis.
The anaerobic intestinal spirochaete Brachyspira pilosicoli colonizes the large intestine of humans, and various species of animals and birds, in which it may induce a mild colitis and diarrhoea. The aim of the current study was to evaluate the use of putative oligopeptide-binding proteins of B. pilosicoli as vaccine components. A partial genome sequence of B. pilosicoli porcine strain 95/1000 was subjected to bioinformatics analysis, and six genes predicted to encode oligopeptide-binding proteins were selected. Following a PCR-based distribution study of the genes across different strains of the spirochaete, they were amplified from B. pilosicoli human strain WesB and cloned in Escherichia coli. The recombinant histidine-tagged proteins were purified and subjected to in vitro and in vivo immunogenicity analysis. Recombinant products (P-1 and P-3) from two genes that were immunogenic and recognized by sera from pigs that had recovered from B. pilosicoli infections were tested in a mouse model of intestinal spirochaetosis. For each recombinant protein, groups of 12 C3H/HeJ mice were vaccinated subcutaneously with 100 microg protein emulsified in Freund's incomplete adjuvant, twice with a 2 week interval. Two weeks later the vaccinated and non-vaccinated control animals were challenged orally with B. pilosicoli strain WesB. Both proteins induced systemic and local colonic IgG antibody responses, and, following experimental infection, the cumulative number of colonization days was significantly (P<0.001) less in both groups of vaccinated mice compared to the control mice. There were significantly (P=0.012) fewer mice colonized in the group vaccinated with P-1 than in the non-vaccinated control group. The results suggest that oligopeptide-binding proteins may have potential for use as components of vaccines for B. pilosicoli.


Pharyngeal Gonorrhea in Heterosexual Male and Female Sex Partners of Persons With Gonorrhea.
Current guidance from the US Centers for Disease Control and Prevention recommends empiric treatment for persons exposed to sexually transmitted infections, including Neisseria gonorrhoeae ( NG ). As an antimicrobial stewardship measure, some clinics now recommend a test and treat strategy, but reliance on urogenital testing only may miss cases. We conducted a descriptive analysis of pharyngeal NG infection in men who have sex with women (MSW) and women seeking care at a sexual health clinic in Seattle, WA, from February 2017 to July 2021 because of sexual contact to a partner diagnosed with gonorrhea. We also explored behavioral factors associated with pharyngeal NG positivity (by culture or nucleic acid amplification test by χ2 analysis. Among 352 NG contacts tested for urogenital or pharyngeal infection, 34% were positive for NG at ≥1 anatomic site (27% for MSW and 40% for women). Among 161 NG contacts tested at the pharynx, 30% (n = 48) were positive: 20% of 54 MSW (n = 11) and 35% (n = 37) of 107 women. If only urogenital testing were performed, 36% of MSW NG infections (n = 5) and 19% of female NG infections (n = 9) would have remained unidentified. Pharyngeal NG is relatively common among MSW and women who have been exposed to NG, and likely represents an underdiagnosed reservoir of NG infection. If empiric treatment is abandoned in favor of testing and treating, testing the throats of heterosexuals will be necessary.


An automated workflow to screen alkene reductases using high-throughput thin layer chromatography.
Synthetic biology efforts often require high-throughput screening tools for enzyme engineering campaigns. While innovations in chromatographic and mass spectrometry-based techniques provide relevant structural information associated with enzyme activity, these approaches can require cost-intensive instrumentation and technical expertise not broadly available. Moreover, complex workflows and analysis time can significantly impact throughput. To this end, we develop an automated, 96-well screening platform based on thin layer chromatography (TLC) and use it to monitor in vitro activity of a geranylgeranyl reductase isolated from Sulfolobus acidocaldarius (SaGGR). Unreduced SaGGR products are oxidized to their corresponding epoxide and applied to thin layer silica plates by acoustic printing. These derivatives are chromatographically separated based on the extent of epoxidation and are covalently ligated to a chromophore, allowing detection of enzyme variants with unique product distributions or enhanced reductase activity. Herein, we employ this workflow to examine farnesol reduction using a codon-saturation mutagenesis library at the Leu377 site of SaGGR. We show this TLC-based screen can distinguish between fourfold differences in enzyme activity for select mutants and validated those results by GC-MS. With appropriate quantitation methods, this workflow can be used to screen polyprenyl reductase activity and can be readily adapted to analyze broader catalyst libraries whose products are amenable to TLC analysis.


Effectiveness of first-aid training on school students in Singur Block of Hooghly District, West Bengal.
First aid is the helping behavior and initial care provided for an acute illness or injury. Students have the potential for changing the health scenario of the society if properly groomed and educated. The objective of the study is to evaluate the effectiveness of educational intervention on the first aid among middle school students of a rural school in West Bengal. A total of 230, 6th and 7th standard students were given a self-administered questionnaire for assessing their baseline knowledge about management of common injuries followed by educational intervention with a systematically devised teaching module during February to March 2016. Post intervention evaluation of their knowledge acquisition was done after 2 weeks with same questionnaire. The baseline knowledge on the management of selected injuries was found to be insufficient among the study subjects. Paired t-test was performed to compare the pre- and post-test scores of knowledge and attitude of the students about first aid, and there was a significant change in knowledge from pretest score (mean = 1.50, standard deviation [SD] =0.47) to posttest score (mean = 6.53, SD = 1.30). To quantify the effectiveness of health education, effect size (Cohen's d) was derived. For knowledge score, Cohen's d was 5.14 with large effect size indicating highly effective impact of the training program. Significant change was also noticed regarding attitude regarding first aid as evident from increase in pretest score (mean = 1.19, SD = 0.96) to posttest score (mean = 3.17, SD = 1.03); Cohen's d was 1.88 with medium effect size. Inculcating first-aid training in the school curriculum can be a fruitful investment in ensuring proper and timely management of illnesses and injuries not only for the school children but also for the community at large.


A Generalized Lichen Planus Following COVID-19 Vaccination: A Case Report.
As part of the efforts to overcome the ongoing coronavirus disease 2019 (COVID-19) pandemic, mass vaccination programs against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been initiated. Since then, an increasing number of cutaneous adverse events associated with the COVID-19 vaccines have been reported. Lichen planus (LP) is a rare inflammatory mucocutaneous disease with various clinical presentations, although uncommon, occurring following vaccination. There have been several cases of LP reported following COVID-19 vaccination. However, there has been no report of generalized LP following the COVID-19 vaccine to our knowledge. Herein, we report a case of generalized LP following the Oxford/AstraZeneca (AZD1222) vaccine. A 68-year-old female presented with widespread, erythematous pruritic papules and plaques on the trunk and both limbs, which developed 2 to 3 days after administration of the AZD1222 vaccine. Histopathological examinations revealed cellular interface dermatitis. The patient was diagnosed with generalized LP and was successfully treated with systemic corticosteroid and cyclosporine. As the vaccination campaign against COVID-19 is ongoing and early recognition and treatment are essential to reduce the morbidity of this condition, clinicians should be aware that LP could follow COVID-19 vaccination regardless of the type of vaccine administered.


Biphenotypic sinonasal sarcoma: demographics, clinicopathological characteristics, molecular features, and prognosis of a recently described entity.
Biphenotypic sinonasal sarcoma (BSNS) is a recently recognized type of sarcoma arising exclusively in the sinonasal tract displaying unique clinical course, histopathology, and genetics. Due to its rarity, only case series and case reports are available. In order to provide an overview of the current understanding of this disease, we present a comprehensive review of the literature and present three previously unreported cases of BSNS. A total of 55 genetically characterized and 41 cases without molecular data were identified in the literature. Two-thirds of patients were female and the peak incidence was in the fifth decade. Fatal outcome was rare (two cases with intracranial extension) and local recurrence occurred in 31.6%, all occurring within 5 years after initial treatment. Histologically, BSNS is highly cellular in the majority of cases and composed of fascicles of spindle cells, with entrapped hyperplastic surface epithelium being a frequent finding. The immunohistochemical profile is characteristic due to the biphasic nature of this lesion, with shared features of both myogenic and neural origin. Rhabdomyoblastic differentiation is apparent in a subset of cases. The most common genetic event is the PAX3-MAML3 fusion (58.6%) but isolated PAX3 rearrangement (19.2%), absence of rearrangements (9.1%), PAX3-FOXO1 (8.1%), PAX3-NCOA1 (4%), and isolated MAML3 rearrangement (2%) have also been reported. In conclusion, the recognition of BSNS is crucial due to its relatively indolent clinical course. A selected immunohistochemical panel and/or molecular confirmation can be used to aid in appropriate diagnosis and consequently in prognostication and to avoid overtreatment with chemotherapy regimens used in its mimics.


Test-retest reliability and responsiveness of a Malay tinnitus questionnaire.
Tinnitus is a common complaint among patients with ear diseases and can be serious if not treated. Recently, a Malay tinnitus questionnaire, known as the "Borang Evaluasi Soal selidik Tinnitus" (BEST) had been developed and preliminarily validated among Malayspeaking population. The aims of the present study were to determine the test-retest reliability and responsiveness of the BEST questionnaire. Forty-six Malay adults (aged 23-74 years) with tinnitus were enrolled. They were instructed to fill in the BEST questionnaire accordingly. After one week, 21 of them were asked to fill in the questionnaire again. The other 25 subjects underwent tinnitus intervention for three months and following this; the BEST was administered to them again. In the test-retest reliability task, the intraclass correlation values obtained were acceptably high (0.70-0.90). After the intervention, significant differences in the BEST result were found in the mind domain, main domain and composite score (p<0.05) with moderate effect sizes (0.61- 0.70). The test-retest reliability of the BEST was found to be good. It also showed good responsiveness to intervention. The clinical usefulness of the BEST in assessing patients with tinnitus was further supported by the present study.


Inducible CD4+LAP+Foxp3- regulatory T cells suppress allergic inflammation.
Regulatory T cells (Tregs) play a critical role in the maintenance of airway tolerance. We report that inhaled soluble Ag induces adaptive Foxp3(+) Tregs, as well as a regulatory population of CD4(+) T cells in the lungs and lung-draining lymph nodes that express latency-associated peptide (LAP) on their cell surface but do not express Foxp3. Blocking the cytokine IL-10 or TGF-β prevented the generation of LAP(+) Tregs and Foxp3(+) Tregs in vivo, and the LAP(+) Tregs could also be generated concomitantly with Foxp3(+) Tregs in vitro by culturing naive CD4(+) T cells with Ag and exogenous TGF-β. The LAP(+) Tregs strongly suppressed naive CD4(+) T cell proliferation, and transfer of sorted OVA-specific LAP(+) Tregs in vivo inhibited allergic eosinophilia and Th2 cytokine expression in the lung, either when present at the time of Th2 sensitization or when injected after Th2 cells were formed. Furthermore, inflammatory innate stimuli from house dust mite extract, nucleotide-binding oligomerization domain containing 2 ligand, and LPS, which are sufficient for blocking airway tolerance, strongly decreased the induction of LAP(+) Tregs. Taken together, we concluded that inducible Ag-specific LAP(+) Tregs can suppress asthmatic lung inflammation and constitute a mediator of airway tolerance together with Foxp3(+) Tregs.


Pharmacy students' knowledge, attitudes, and behaviors regarding emergency contraception.
To determine pharmacy students' knowledge, attitudes, and behaviors regarding emergency contraception. A cross-sectional survey was conducted among a convenience sample of students prior to a regular class period. The 16-item survey instrument included both multiple-choice and true/false questions to assess knowledge and Likert-type scale questions regarding attitudes and behaviors. Frequency and descriptive statistics were calculated for all variables. Three hundred one pharmacy students were surveyed. Eighty-seven percent knew that Plan B had been approved by the Food and Drug Administration (FDA) for nonprescription use, yet 33% believed that it worked by disrupting a newly implanted ovum. On a scale from 1-5 on which 5 = strongly agree, the mean item score was 1.5 for whether nonprescription emergency contraception should be available without counseling by a pharmacist, yet only 26.7% believed they were competent instructing patients on the use of emergency contraception. Additional education is needed to prepare pharmacy students to provide informed pharmaceutical care to patients seeking emergency contraception, especially given the passage of legislation making the pharmacy the point of access for some emergency contraception products.


Bispectral analysis and model validation of texture images.
Statistical approaches to texture analysis and synthesis have largely relied upon random models that characterize the 2-D process in terms of its first- and second-order statistics, and therefore cannot completely capture phase properties of random fields that are non-Gaussian and/or asymmetric. In this paper, higher than second-order statistics are used to derive and implement 2-D Gaussianity, linearity, and spatial reversibility tests that validate the respective modeling assumptions. The nonredundant region of the 2-D bispectrum is correctly defined and proven. A consistent parameter estimator for nonminimum phase, asymmetric noncausal, 2-D ARMA models is derived by minimizing a quadratic error polyspectrum matching criterion. Simulations on synthetic data are performed and the results of the bispectral analysis on real textures are reported.


When to start and when to stop antifibrotic therapies.
Idiopathic pulmonary fibrosis (IPF) is characterised by progressive changes of the lung architecture causing cough and dyspnoea and ultimately leading to lung failure and death. Today, for the first time, two drugs that may reduce the inexorable progression of the disease are available, suggesting that treatment with specific drugs for IPF should be started as soon as diagnosis is made. This applies to any disease and particularly to IPF, which is marked by a 5-year survival comparable or even worse than many cancers. However, despite common sense and even worse, in spite of scientific data coming from clinical trials, post hoc analysis, long-term safety studies and real-life experiences, the question of when to start and when to stop treatment with antifibrotics is still debated. In IPF, particularly when the disease is diagnosed at an early stage, "wait and watch" behaviour is not rare to observe. This is largely due to the lack of awareness of both patients and clinicians regarding the progression of the disease and its prognosis. Another important issue is when treatment should be stopped. In general, there are two main reasons to stop a therapy: unbearable side-effects and/or lack of efficacy. According to current (although preliminary) evidence, antifibrotic drugs should not be discontinued except for safety issues.


[Conservative approach in major renal trauma].
Genitourinary trauma amount to an 8-10% of abdominal trauma with the kidney being the most affected organ in 50% of cases, especially the left one. The choice of treatment will depend on the kind of lesion found in the affected renal unit and on the patient's clinical conditions. The aims of this study are twofold: to determine the applicability of conservative treatment in major renal trauma and to assess the evaluation and emergence of possible complications. We have analysed 309 cases of renal trauma dealt with in our department between January 1984 and January 2006, analyzing such variables as the etiology of the trauma, associated lesions in other organs, the therapeutic approach adopted as well as the presence of complications, both in the long and short run. Out of a total of 309 renal trauma analyzed, a 94.1% (291 cases) were blunt renal trauma. The distribution by grade was: Grade I, 213 cases (69%); Grade II, 39 cases (12.6%); Grade III/IV, 32 cases (10.3%); Grade V, 25 cases (8%). We have given a conservative approach in the 84.6% of the grade III/IV cases (24 cases). 4 grade III nephrectomies were carried out in the Emergency Room because of haemodynamic instability, other 4 grade IV nephrectomies were done for the same reason, one of which was a partial nephrectomy, 48-72 hours after the trauma. The treatment for grade V was nephrectomy in 67%. According to our experience and in the light of the results obtained, we consider the conservative approach adequate for major renal trauma as long as the patient is haemodynamically stable.


"Day-to-day, it's a roller coaster. It's frustrating. It's rewarding. It's maddening and it's enjoyable": A qualitative investigation of the lived experiences of addiction counselors.
Psychologists in medication for addiction treatment (MAT) settings routinely oversee the work of addiction counselors as supervisors, administrators, and human resource specialists. Limited research has explored the lived experiences of counselors who work in programs that have scaled-up MAT in response to the opioid crisis in the U.S. Thirty-one addiction counselors who worked in MAT programs that had scaled-up treatment capacity were interviewed about 3 facets of their lived experiences: work roles, work motivation, and perceived responses of others to their work. Interviews were taped and transcribed. An interdisciplinary team reviewed and coded the transcripts using grounded theory analysis. The main work roles that emerged were counselor, educator, and advocate. Counselors described multiple factors related to intrinsic motivation for their work: family and personal history, altruism, enjoyment of challenges and client complexity, and witnessing and facilitating change. Factors related to extrinsic motivation were workplace opportunities and positive feedback. The main themes concerning responses of nonclients were positive feedback; others' narratives; negative feedback focused on the stigma associated with the treatment, the clients who receive it, and the counselors who provide it; and responses to anticipated negative feedback. Responses from clients were largely positive and focused on appreciation and respect. Psychologists in MAT settings can enhance the lived experiences of addiction counselors by helping them to savor positive feedback from clients and others, to recognize and appreciate their unique skillsets, and to recognize and address (not internalize) the multiple sources of stigma they encounter as addiction counselors. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Hemodialysis and CAPD--are they comparable?
I have made comparisons of thrice weekly HD (not daily HD) and PD (mainly CAPD). In terms of patient survivals, there is no proven modality advantage. In terms of cost and quality of life, PD probably has advantages in many patients. With a tendency towards earlier initiation of dialysis and incremental prescriptions to achieve a targeted amount of small-solute clearances, PD probably has cost and technical advantages.


Genome sequencing reveals extraordinary cephalic horns in the Madagascan dung beetle genus Helictopleurus (Coleoptera, Scarabaeinae): insight from a revision of fungicola species group.
In this study, we test and corroborate the phylogenetic position of Heterosyphus within Helictopleurus using mitogenomes and nuclear loci. Our recent samplings revealed that males of the former Heterosyphus sicardi Paulian, 1975 (today under Helictopleurus d'Orbigny, 1915) have extraordinary bilateral clypeal horns which are exclusive within the genus. We provide a taxonomic review of the fungicola species group of Helictopleurus and discuss the systematic position of H. sicardi within the group. The male phenotype of H. sicardi is described and photographs of the body and genitalia of the members of the fungicola group are given, as well as a diagnostic key to species of the group. Helictopleurus fungicola peyrierasi is considered to be a distinct species within the genus (H. peyrierasi stat. rest.). Helictopleurus pluristriatus d'Orbigny, 1915 syn. nov. is established as a junior synonym of H. fungicola (Fairmaire, 1899).


Prognostic value of early response assessment using (18F)FDG-PET in patients with advanced non-small cell lung cancer treated with tyrosine-kinase inhibitors.
The purpose of this meta-analysis was to determine the prognostic value of early response assessment using (18F)fluorodeoxyglucose (FDG)-positron emission thermography (PET) in patients with advanced non-small cell lung cancer (NSCLC) treated with tyrosine-kinase inhibitors (TKIs). MEDLINE, PubMed, Cochrane, EMBASE, and Google Scholar databases were searched until August 1, 2016 using the keywords non-small cell lung carcinoma, positron-emission tomography, fluorodeoxyglucose, prognosis, disease progression, survival, erlotinib, gefitinib, and afatinib. Inclusion criteria were studies of patients with stage III or IV NSCLC treated with a TKI and had response assessed by FDG-PET. Outcome measures were overall survival (OS) and progression-free survival (PFS). Of the 167 articles identified, 10 studies including 302 patients were included in the analysis. In 8 studies, patients were treated with erlotinib, and in 2 they were treated with gefitinib. The overall analysis revealed that early metabolic response was statistically associated with improved OS (HR=0.54; 95% CI 0.46 to 0.63; p<0.001), and with longer PFS (HR=0.23; 95% CI 0.17 to 0.33; p<0.001). Early response of patients with NSCLC treated with TKIs identified on FDG-PET is associated with improved OS and PFS.


A Cyclic Peptide Inhibitor of the iNOS-SPSB Protein-Protein Interaction as a Potential Anti-Infective Agent.
SPRY domain- and SOCS box-containing proteins SPSB1, SPSB2, and SPSB4 interact with inducible nitric oxide synthase (iNOS), causing the iNOS to be polyubiquitinated and targeted for degradation. Inhibition of this interaction increases iNOS levels, and consequently cellular nitric oxide (NO) concentrations, and has been proposed as a potential strategy for killing intracellular pathogens. We previously described two DINNN-containing cyclic peptides (CP1 and CP2) as potent inhibitors of the murine SPSB-iNOS interaction. In this study, we report the crystal structures of human SPSB4 bound to CP1 and CP2 and human SPSB2 bound to CP2. We then used these structures to design a new inhibitor in which an intramolecular hydrogen bond was replaced with a hydrocarbon linkage to form a smaller macrocycle while maintaining the bound geometry of CP2 observed in the crystal structures. This resulting pentapeptide SPSB-iNOS inhibitor (CP3) has a reduced macrocycle ring size, fewer nonbinding residues, and includes additional conformational constraints. CP3 has a greater affinity for SBSB2 ( KD = 7 nM as determined by surface plasmon resonance) and strongly inhibits the SPSB2-iNOS interaction in macrophage cell lysates. We have also determined the crystal structure of CP3 in complex with human SPSB2, which reveals the structural basis for the increased potency of CP3 and validates the original design.


Breath tests with stable isotopes: have they a role in liver transplantation?
Evaluation of liver function is crucial in the overall management of patients with liver disease. In particular, patients with end-stage liver disease need accurate prognostic indicators to plan liver transplantation, and in this case, to manage their presence in the waiting list. Availability of predictors of clinical outcome is further essential after liver transplant, mainly to correctly diagnose and adequately treat complications, such as acute rejection, drug toxicity, liver dysfunction. Breath tests using labelled substrates selectively metabolized within the liver may represent an accurate diagnostic and prognostic tool in these clinical conditions, possibly with an adjuntive role to the most commonly used prognostic models (Child-Pugh and MELD scores). Promising results have been in fact recently obtained by the use of different substrates (aminopyrine, methacetin, erythromycin, methionine) which explore different metabolic function of the hepatocyte. The usefulness of breath tests has been documented in liver disease patients both before and after liver transplantation, in the early as well as in the late phase.


A rapid method to non-invasively estimate training-induced hemodynamic changes in top-level athletes.
The estimation of cardiovascular adaptation to exercise provides valuable information on training status. However, albeit of interest, it has been rarely used in athletes, being the current non-invasive techniques expensive and requiring specialist expertise. Recently, a new bioreactance-based method is available; however, no data have been collected in trained athletes. The aim of this prospective, longitudinal study was to evaluate by bioreactance the training-induced hemodynamic changes. Ten top-level basketball players were enrolled. Bioreactance analysis was performed at the beginning and after 5 months of training and an echocardiographic examination was simultaneously performed. After training, no significant differences were found in cardiac output (P=0.68) and in cardiac index (P=0.78). Diastolic blood pressure significantly decreased (P<0.05) and a non-significant decrease in peripheral resistance was observed (P=0.57). A significant increase in thoracic fluid content was observed after training (P<0.05). While absolute values were different between bioreactance and echocardiography, a similar trend of exercise-induced hemodynamic changes was found. Both before and after training, an inverse relationship between TPR and CO (r=-0.818, P<0.005; r=-0.891, P=0.001, respectively) and between TPR and SV was found (r=-0.794, P=0.006; r=-0.745, P<0.05, respectively). Bioreactance-derived method represents a novel non-invasive technique able to provide a rapid and comprehensive evaluation of cardiovascular response to training. Using trends rather than single, isolated measurements, this method could provide useful data on the cardiovascular response to training in competitive athletes.


Determination of Temperature Dependent Growth Parameters in Psychrotrophic Pathogen Bacteria and Tentative Use of Mean Kinetic Temperature for the Microbiological Control of Food.
Temperature is the main factor to control the microbial growth in perishable foods. The psychrotrophic pathogen bacteria are microorganisms of concern for food products with extended shelf life in chilling conditions. The aims of this work were two. Firstly, to evaluate growth behavior of Aeromonas hydrophila DSM-30187, Listeria monocytogenes DSM-20600, and Yersinia enterocolitica DSM-27689 strains, at different temperatures (4, 7, 10, 15, 25, and 30°C) and starting cell concentrations (10 and 106 CFU/mL), in order to determine the activation energies (E a) of the relevant lag phases and growth rates. Secondly, to investigate if Mean Kinetic Temperature (MKT) might be applied in recording temperature devices to alert a thermal abuse in a management control system for food safety. As expected, lag phase and growth rate proved to be heavily affected by temperature whereas the inoculum size did not. The E a values involved in the duration of latent periods, calculated on the basis of the Arrhenius model, were comparable for A. hydrophila and L. monocytogenes strains (from 21.3 to 24.4 kcal/mol), while significantly differed for Y. enterocolitica (16.6 kcal/mol). The E a values of growth rates were similar for A. hydrophila and L. monocytogenes strains (from 20.9 to 21.1 kcal/mol), while were considerably lower for Y. enterocolitica (from 14.2 to 16.7 kcal/mol). The use of MKT is widespread and well-accepted in pharmaceutical field as convenient method for estimating drugs degradation in relation to storage temperature. The E a value of the lag phase found for L. monocytogenes (23.9 ± 1.2 kcal/mol) was included in the MKT formula. In this work, the air temperature of two chilling rooms was monitored during the normal operating activity in a catering company for a period of 8 months. The MKT profiles were then compared with those of mean temperatures in different conditions (short or prolonged events of thermal abuse) with the purpose to evaluate if it may be applicable to reduce false alarms without lowering the safety level of stored food.


Controlled biological response on blends of a phosphorylcholine-based copolymer with poly(butyl methacrylate).
Phosphorylcholine (PC)-based polymers have been used in a variety of medical device applications to improve biocompatibility. Here, solutions containing poly(butyl methacrylate) (PBMA) and 2-methacryloyloxyethyl phosphorylcholine-co-lauryl methacrylate (MPC-co-LMA(2)) copolymer were spin-coated onto glass coverslips at various ratios ranging from 5:1 to 1:0 for each of the two components, respectively. The resulting blend coatings were shown to be phase-separated on the nanometre-scale by atomic force microscopy, the PC copolymer within the blend being preferentially expressed at the surface. The adsorption of two key blood proteins, fibrinogen and albumin were investigated using surface plasmon resonance as an indicator of biocompatibility. The adsorption of protein to a biomaterials' surface can then stimulate further biological responses. This study therefore, also investigates the materials ability to elicit an inflammatory response by studying the adhesion of human mononuclear cells to the material surface. The materials ability to support the adhesion and growth of other tissue cells was also evaluated, looking specifically at the adhesion and proliferation of rabbit corneal epithelial cells. Results suggest that the adsorption of proteins and the adhesion of both corneal epithelial cells and mononuclear cells are dependent on the composition of the PBMA:MPC-co-LMA(2) copolymer.


Urinary continence after radical prostatectomy: the Columbia experience.
We determine the incidence of urinary incontinence after radical prostatectomy and the factors that may influence this incidence. A total of 615 men who underwent radical retropubic prostatectomy performed by 1 of us (C. A. O. or M. C. B.) at our center between 1988 and 1996 were mailed a questionnaire regarding preoperative and postoperative voiding habits. Data collected included preoperative and postoperative continence status, interval to postoperative continence status, associated urinary symptoms, willingness to undergo radical prostatectomy again if given the chance and additional postoperative procedures. Patient age, date of surgery and duration of followup were also noted. Of the 615 patients 480 (78.2%), a mean of 62.6 years old, responded to the questionnaire. Mean followup was 3.3 years (range 1 to 8.8). Continence was defined as no regular use of pads. Of the respondents 91.8% were considered continent, 92% had achieved final continence status by 6 months postoperatively, 10.6% required 1 or more additional procedures related to urinary control and 90% would undergo surgery again if given the chance. Of the patients considered incontinent postoperatively 44% had associated urgency. Age, year of surgery and preoperative urinary leakage or post-void dribbling had no significant impact on postoperative continence status. Using an anonymous self-administered questionnaire we found an 8.2% incontinence rate after radical prostatectomy. This rate was similar to that in large, single institutional studies in which physician interview was used to elicit responses but significantly less than that in a national sample of Medicare patients also given a self-administered questionnaire. With minimal potential for adverse consequences in the hands of experienced surgeons, radical prostatectomy remains well tolerated with excellent patient satisfaction.


Photon upconversion utilizing energy beyond the band gap of crystalline silicon with a hybrid TES-ADT/PbS quantum dots system.
The recent introduction of inorganic semiconductor quantum dots (QDs) as triplet sensitizers for molecular semiconductors has led to significant interest in harvesting low energy photons, which can then be used for photon upconversion (PUC), via triplet-triplet annihilation (TTA). A key goal is the harvesting of photons from below the bandgap of crystalline silicon 1.12 eV (≈1100 nm) and their upconversion into the visible region. In practice, the systems demonstrated so far have been limited to harvesting photons with energies above 1.2 eV (≈1 μm), due to two reasons: firstly the need to use transmitter ligands which allow efficient energy harvesting from the QD but introduce an energy loss of larger than 200 meV in transmission from the QD to the annihilator, and secondly due to the use of molecules such as tetracene which cannot accept smaller energy than 1.2 eV. Here, we introduce a new strategy to overcome these difficulties by using a low energy triplet annihilator that also harvests excitations efficiently from QDs. Specifically, we show that 5,11-bis(triethylsilylethynyl)anthradithiophene (TES-ADT, triplet energy of 1.08 eV: ca. 1150 nm) functions as a triplet annihilator (20% TTA efficiency) while also rapidly extracting triplet excitons from lead sulfide (PbS) QDs with a rate constant of k = ca. 2 × 10-8 s-1 with an excitation at 1064 nm. This rate is consistent with an orbital overlap between TES-ADT and PbS QDs, which we propose is due to the thiophene group of TES-ADT, which enables a close association with the PbS surface, allowing this system to function both as annihilator and transmitter. Our results pave the way for the design of triplet annihilators that can closely associate with the QD surface and harvest low energy excitons with minute losses in energy during the TET process, with the ultimate goal of efficiently utilizing photon energy beyond the bandgap of crystalline silicon.


Cloning of the Lycopene β-cyclase Gene in Nicotiana tabacum and Its Overexpression Confers Salt and Drought Tolerance.
Carotenoids are important pigments in plants that play crucial roles in plant growth and in plant responses to environmental stress. Lycopene β cyclase (β-LCY) functions at the branch point of the carotenoid biosynthesis pathway, catalyzing the cyclization of lycopene. Here, a β-LCY gene from Nicotiana tabacum, designated as Ntβ-LCY1, was cloned and functionally characterized. Robust expression of Ntβ-LCY1 was found in leaves, and Ntβ-LCY1 expression was obviously induced by salt, drought, and exogenous abscisic acid treatments. Strong accumulation of carotenoids and expression of carotenoid biosynthesis genes resulted from Ntβ-LCY1 overexpression. Additionally, compared to wild-type plants, transgenic plants with overexpression showed enhanced tolerance to salt and drought stress with higher abscisic acid levels and lower levels of malondialdehyde and reactive oxygen species. Conversely, transgenic RNA interference plants had a clear albino phenotype in leaves, and some plants did not survive beyond the early developmental stages. The suppression of Ntβ-LCY1 expression led to lower expression levels of genes in the carotenoid biosynthesis pathway and to reduced accumulation of carotenoids, chlorophyll, and abscisic acid. These results indicate that Ntβ-LCY1 is not only a likely cyclization enzyme involved in carotenoid accumulation but also confers salt and drought stress tolerance in Nicotiana tabacum.


Single-Molecule Characterization of Drug Delivery Systems.
Delivery of the drug to a desired point of body and controlled release of the therapeutic agent are important features, provided by drug delivery systems (DDSs), for development of today's effective medicines. A variety of nanomaterials or nanomolecules such as lipids/liposomes, nucleic acids, peptides/proteins, composites, polymers, or carbon nanotubes can be used as DDSs. Single-molecule characterization of these small materials in terms of their size, shape, surface, encapsulation efficiency, as well as interaction with the drug-receiving cell has importance for their efficiency. The loading, distribution, or leakage of the drug as well as its interaction with DDS should also be characterized. Although diverse techniques are present for characterization of specific DDS material, methods such as electron microscopy and fluorescence microscopy are widely used. In this review, the current methodologies utilized for the single-molecule characterization of mostly preferred DDS materials were presented.


Role of macrophages in the biological reaction to wear debris from joint replacements.
Normal usage of total joint replacements results in the production of wear debris and other byproducts. In particular, polyethylene particles are heavily involved in the stimulation of local and systemic biological reactions resulting in chronic inflammation, periprosthetic bone resorption (osteolysis), and, eventually, implant loosening. As sentinels of the innate immune system, cells of the monocyte/macrophage lineage initiate the inflammatory cascade that leads to osteolysis. The biological processes involved are complex, based on the unique properties of the monocytes/macrophages, including sensing, chemotaxis, phagocytosis, and adaptive stimulation. The interaction with wear debris triggers the release of pro-inflammatory factors, such as TNF-α, IL-1, and others, pro-osteoclastic factors such as RANKL, and chemokines, such as MCP-1 and MIP-1, all being crucial to the recruitment, migration, differentiation, and ultimately activation of bone resorbing osteoclasts. In parallel, other distinct macrophage populations inhibit inflammation and mitigate its consequences on the bone-implant interface. Here, the role of the monocyte/macrophage cell lineage in the initiation and maintenance of the host inflammatory response to wear debris and subsequent periprosthetic osteolysis is presented.


Infections of pediatric cerebrospinal fluid shunts related to fundoplication and gastrostomy.
There is conflicting information in the literature regarding the increased risk of ventriculoperitoneal (VP) shunt infection after abdominal surgical procedures such as gastrostomy tube (GT) placement and Nissen fundoplication (NF) in the young patient. To further elucidate this potential association, the authors reviewed their institutional experience with such cases. The authors retrospectively reviewed the records of all patients with shunted hydrocephalus who also underwent NF procedures and/or GT placements over a 9-year period. During this 9-year period, 3065 cerebrospinal fluid (CSF) shunts were placed and 1630 NF procedures/GT placements were performed. Ninety-six patients were identified who received both a CSF shunt and NF procedures/GT placements. Seventy-nine patients had a functioning VP shunt (without recent [< 6 months] CSF infection or shunt revision) at the time of their abdominal procedure (NF procedure or GT placement). Of this latter cohort, there were 38 males and 41 females with a mean age of 6.4 months; 12.7% of these patients developed a shunt infection and 60% of these infections were due to Staphylococcus species. Based on this study, an NF procedure/GT placement in a child with a VP shunt appears to carry approximately the same risk of shunt infection as a shunt placement operation. Moreover, the microbiology observed in these patients with infection did not differ significantly from the usual microorganisms responsible for VP shunt infections in infants/neonates. Finally, but not conclusively, an open NF procedure/GT placement may carry a higher infection risk than a laparoscopic-assisted NF procedure/GT placement.


DNA diagnosis for hereditary cerebral hemorrhage with amyloidosis (Dutch type)
Hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D) is tightly linked to the Alzheimer amyloid precursor protein gene on chromosome 21, which codes for the amyloid beta-protein. A point mutation detected at position 1852 of the amyloid precursor protein gene in four HCHWA-D patients was hypothesized to be the basic defect. This study proves that 22 HCHWA-D patients from three pedigrees all carry this point mutation, whereas the mutation is absent in escapees from the HCHWA-D families as well as in randomly selected Dutch individuals. A mutation-specific oligonucleotide is now available for the confirmation of the HCHWA-D diagnosis. Therefore, presymptomatic testing and prenatal evaluation of individuals at risk in the HCHWA-D families is now feasible.


An event generator for same-sign W-boson scattering at the LHC including electroweak corrections.
In this article we present an event generator based on the Monte Carlo program Powheg in combination with the matrix-element generator Recola. We apply it to compute NLO electroweak corrections to same-sign W-boson scattering, which have been shown to be large at the LHC. The event generator allows for the generation of unweighted events including the effect of the NLO electroweak corrections matched to a QED parton shower and interfaced to a QCD parton shower. In view of the expected experimental precision of future measurements, the use of such a tool will be indispensable.


The Beneficial Effect of Beta-Blockers in Patients With Cirrhosis, Portal Hypertension and Ascites.
Patients with cirrhosis and portal hypertensive complications have reduced survival. As such, it has been suggested that nonselective beta-blocker therapy in patients with advanced ascites is harmful. The aim of this study was, therefore, to determine the risk of mortality in patients with cirrhosis and ascites taking nonselective beta-blocker therapy for the prevention of variceal hemorrhage. This study was a retrospective analysis of 2,419 patients with cirrhosis and portal hypertension admitted to Parkland Memorial Hospital (a university-affiliated county teaching hospital) from 2003-2010. Patients were subdivided into those with varices only, ascites only and those with both varices and ascites. The primary outcome measure for this study was all-cause in-hospital mortality. Overall, 68 of 1,039 (6.5%) patients taking beta-blockers died during their hospitalization, while 223 of 1,380 (16.2%) patients not taking beta-blockers died (P < 0.001). Beta-blocker use was also assessed in specific cohorts; mortality was 21.1% in patients with severe ascites with varices who were not taking beta-blockers compared with 8.9% in patients who were taking beta-blockers (P = 0.05). Overall, fewer patients taking beta-blockers died compared with those not taking beta-blockers in patients with varices only (6.4% versus 12.1%) and those with ascites with or without varices (6.6% versus 18.1%) (P < 0.001). Mortality was lower in patients with cirrhosis and portal hypertension taking nonselective beta-blockers than in those not taking beta-blockers. The use of nonselective beta-blockers provided a significant survival benefit in patients with all grades of ascites, including those with severe ascites.


Monte Carlo determination of inhomogeneity effect on gamma-ray detection efficiency in soil samples.
Inhomogeneity effect on full energy peak (FEP) efficiency in a soil sample was determined using the Monte Carlo simulation technique. The dependence of the FEP efficiency on the homogeneity in the soil was obtained for some particular photon energies ranging from 60 keV to 2 MeV and, as a result, the corresponding correction factors were obtained. This effect was more significant at lower energies and for higher inhomogeneity rates.


Incidence of endemic Opisthorchis viverrini infection in a village in northeast Thailand.
Incidence, measured as the proportion of persons whose stools become positive within one year, was studied in endemic Opisthorchis viverrini, the human liver fluke, in a northeastern Thai village over a two-year period. Incidence was higher in males than in females, especially in children under five years of age. It was at least 47% overall in the first year of the study, but declined to below 20% per year in the second. This is attributed to drying of a local water reservoir and decline in availability of infective stages in fish. The fluctuation of incidence is probably due to the large variations in rainfall from year to year. The rate of reversion from positive to negative varied from 2% to 6% per year.


The effects of holistic health group interventions on improving the cognitive ability of persons with mild cognitive impairment: a randomized controlled trial.
Persons with mild cognitive impairment (PwMCI) are at a higher risk of developing dementia than those without cognitive impairment. This research study aims to evaluate the effectiveness of a holistic health group intervention, which is based on the holistic brain health approach as well as an Eastern approach to health care, on improving the cognitive ability of Chinese PwMCI. In a randomized controlled trial (RCT), 38 Chinese PwMCI were randomly assigned to either a 10-session holistic health intervention group or the control group. The holistic health treatment group attempted to promote the acceptance of their illness, enhance memory and coping skills, develop a positive lifestyle, maintain positive emotions, and facilitate emotional support among participants. The 10-session holistic health group intervention was structured, with each session conducted once per week and ~90 minutes in length. Control group patients and their family caregivers received standardized basic educational materials that provided basic information on cognitive decline for them to read at home. The Montreal Cognitive Assessment (MoCA) test was used to assess the cognitive ability of PwMCI in the pre- and posttreatment periods by a research assistant who was blind to the group assignment of the participants. The paired-samples t-test indicated that the treatment group (n=18) showed significant improvement in the MoCA score, whereas the control group (n=20) did not. Moreover, 2×2 (group × time) repeated-measures analysis of covariance (ANCOVA) demonstrated that the holistic health group treatment was significantly more effective than the control intervention in improving the MoCA score, with a moderate effect size, and improving the delayed recall (ie, short-term memory), with a strong effect size, after controlling for age, sex, education, and marital status. This present RCT provides evidence to support the feasibility and effectiveness of the holistic health group intervention in improving the cognitive and short-term memory abilities of PwMCI.


Towards Identifying Genetic Biomarkers for Gastrointestinal Dysfunction in Autism.
This study investigated genetic biomarkers for gastrointestinal dysfunction symptoms in order to provide further information on the genetic risk for GI dysfunction associated with autism. The single nucleotide polymorphisms of sixty participants with autism and/or gastrointestinal dysfunction were analyzed. The autism group had a moderate statistical significance for the Prolactin (PRL) (OR 6.35, p value 0.069) and Interleukin 10 (IL-10) (OR 0.25, p value 0.087) SNPs. The GI dysfunction group had a strong statistical significance for the Cluster of Differentiation 38 (CD38) (OR 6.88, p value 0.005) and oxytocin receptor (OXTR) (OR 0.27, p value 0.036) SNPs. The potential use of PRL, IL-10, CD38, and OXTR SNP expression as biomarkers for GI dysfunction in autism warrants further research.


Understanding the Factors that Impact Effective Uptake and Integration of Health Programs in South African Primary Health Care Clinics.
Introduction : There is an increasingly urgent gap in knowledge regarding the translation of effective HIV prevention and care programming into scaled clinical policy and practice. Challenges limiting the translation of efficacious programming into national policy include both the paucity of proven efficacious programs that are reasonable for clinics to implement and the difficulty in moving a successful program from research trial to scaled programming. This study aims to bridge the divide between science and practice by exploring health care providers' views on what is needed to integrate of HIV programming into clinic systems. Methods : We conducted 20 in-depth interviews with clinic managers and clinic program implementing staff and 5 key informant interviews with district health managers overseeing programming in the uMgungundlovu District of KwaZulu-Natal Province, South Africa. Qualitative data were analyzed using a template approach. A priori themes were used to construct templates of relevance including current care context for HIV and past predictors of successful implementation. Data were coded and analyzed in accordance with these templates. Results : Heath care providers identified three main factors that impact integration of HIV programming into general clinical care: perceived benefits, resource availability, and clear communication. The perceived benefits of HIV programs hinged on the social validation of the program by early adopters. Wide program availability and improved convenience for providers and patients increased perceived benefit. Limited staffing capacity and a shortage of space were noted as resource constraints. Programs that specifically tackled these constraints through, for example clinic decongestion, were reported as being the most successful. Clear communication with all entities involved in clinic-based programs, some of which include external partners, was noted as central to maximizing program function and provider uptake. Conclusions : Amid the COVID-19 pandemic, new programs are already being developed for implementation at the primary health care level. A better understanding of the factors which both facilitate and prevent programmatic success will improve public health outcomes. Implementation is likely to be most successful when programs capitalize on endorsements from early adopters, tackle resource constraints, and foster greater communication among partners responsible for implementation.


Phonological progress during the first 2 years of stuttering.
This report is the third in a series on phonological impairment in children who stutter, comparing its extent in those whose stuttering will be persistent with those in whom that disorder will disappear spontaneously. The first (E. P. Paden & E. Yairi, 1996) compared small groups of these children with normally fluent children of the same ages and sex. The second (E. P. Paden, E. Yairi, & N. G. Ambrose, 1999) compared the phonological abilities evidenced soon after onset of stuttering for 84 young children. In that study, the mean level of phonological skills of the 22 participants whose stuttering eventually persisted for at least 4 years was found to be significantly poorer than that of 62 others whose stuttering would disappear without fluency intervention before that time. In the present study, recorded performances of the same 84 children, made 1 and 2 years later, were similarly evaluated to determine how their phonological development progressed after the initial visit. Results of assessment at the 1-year visit showed that the mean difference between the two groups of children was no longer significant. The children whose stuttering would persist had improved more phonologically than had those who would recover from stuttering. At the 2-year visit, the mean percentage of phonological error for the two groups was identical. Furthermore, at this assessment, only 3 of the children in the Persistent group and 11 of those in the Recovered group had not essentially mastered all of the 10 basic patterns of phonology that were the focus of our evaluation. The findings concerning the longitudinal covariance of stuttering and phonological skills provide information that should be considered in any attempt to explain the relation between the two.


How many species are infected with Wolbachia?--A statistical analysis of current data.
Wolbachia are intracellular bacteria found in many species of arthropods and nematodes. They manipulate the reproduction of their arthropod hosts in various ways, may play a role in host speciation and have potential applications in biological pest control. Estimates suggest that at least 20% of all insect species are infected with Wolbachia. These estimates result from several Wolbachia screenings in which numerous species were tested for infection; however, tests were mostly performed on only one to two individuals per species. The actual percent of species infected will depend on the distribution of infection frequencies among species. We present a meta-analysis that estimates percentage of infected species based on data on the distribution of infection levels among species. We used a beta-binomial model that describes the distribution of infection frequencies of Wolbachia, shedding light on the overall infection rate as well as on the infection frequency within species. Our main findings are that (1) the proportion of Wolbachia-infected species is estimated to be 66%, and that (2) within species the infection frequency follows a 'most-or-few' infection pattern in a sense that the Wolbachia infection frequency within one species is typically either very high (>90%) or very low (<10%).


Early life factors associated with incidence of physician-diagnosed asthma in preschool children: results from the Canadian Early Childhood Development cohort study.
Background. Asthma is a common childhood illness. The objective of this study is to determine the incidence of physician-diagnosed asthma in preschool years and its relationship to host, prenatal and postnatal factors, early childhood factors, parental factors, household factors and demographic factors. Methods. The study sample was comprised of 8,499 infants and toddlers (<2 years at baseline) enrolled in the Canadian Early Childhood Development Study. Incidence of asthma was determined when the children were in preschool age (2 to 5 years). Results. The 4-year cumulative incidence at preschool age was 13.7% for physician-diagnosed asthma. History of early childhood wheezing before 2 years of age was a significant risk factor for incidence of asthma in preschool years (hazard ratio (HR): 2.32; 95% confidence interval (CI): 2.04-2.65). Factors that were protective for the development of asthma were breastfeeding more than 3 months (HR: 0.82; 95% CI: 0.69-0.97); history of nose or throat infection often in childhood (HR: 0.79; 95% CI: 0.67-0.93); early daycare attendance (HR: 0.85; 95% CI: 0.74-0.98); presence of two or more siblings at birth, (HR: 0.79; 95% CI: 0.64-0.97); and dwelling in rural non- central metropolitan areas (HR: 0.81; 95% CI: 0.69-0.95). Male sex, low birth weight, childhood allergy, single parent, maternal smoking during pregnancy, maternal medication use, parental atopy, and low SES at baseline were significant risk factors for the incidence of physician-diagnosed asthma in preschool years. Conclusion. This study emphasizes the role of wheezing in infant and toddler age on early onset of asthma during preschool years. The results also provide additional importance of early exposures to environmental factors such as early infections, daycare attendance, and rural environment in the development of proper immune dynamics to prevent asthma.


How well do rudimentary plasticity rules predict adult visual object learning?
A core problem in visual object learning is using a finite number of images of a new object to accurately identify that object in future, novel images. One longstanding, conceptual hypothesis asserts that this core problem is solved by adult brains through two connected mechanisms: 1) the re-representation of incoming retinal images as points in a fixed, multidimensional neural space, and 2) the optimization of linear decision boundaries in that space, via simple plasticity rules applied to a single downstream layer. Though this scheme is biologically plausible, the extent to which it explains learning behavior in humans has been unclear-in part because of a historical lack of image-computable models of the putative neural space, and in part because of a lack of measurements of human learning behaviors in difficult, naturalistic settings. Here, we addressed these gaps by 1) drawing from contemporary, image-computable models of the primate ventral visual stream to create a large set of testable learning models (n = 2,408 models), and 2) using online psychophysics to measure human learning trajectories over a varied set of tasks involving novel 3D objects (n = 371,000 trials), which we then used to develop (and publicly release) empirical benchmarks for comparing learning models to humans. We evaluated each learning model on these benchmarks, and found those based on deep, high-level representations from neural networks were surprisingly aligned with human behavior. While no tested model explained the entirety of replicable human behavior, these results establish that rudimentary plasticity rules, when combined with appropriate visual representations, have high explanatory power in predicting human behavior with respect to this core object learning problem.


Role of cholangiocytes in primary biliary cirrhosis.
Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by selective destruction of intrahepatic cholangiocytes. Mechanisms underlying the development and progression of the disease are still controversial and largely undefined. Evidence suggests that PBC results from an articulated immunologic response against an immunodominant mitochondrial autoantigen, the E2 component of the pyruvate dehydrogenase complex (PDC-E2); characteristics of the disease are also the presence of disease-specific antimitochondrial autoantibodies (AMAs) and autoreactive CD4 and CD8 T cells. Recent evidence suggests that cholangiocytes show specific immunobiological features that are responsible for the selective targeting of those cells by the immune system. The immune reaction in PBC selectively targets small sized, intrahepatic bile ducts; although a specific reason for that has not been defined yet, it has been established that the biliary epithelium displays a unique heterogeneity, for which the physiological and pathophysiological features of small and large cholangiocytes significantly differ. In this review article, the authors provide a critical overview of the current evidence on the role of cholangiocytes in the immune-mediated destruction of the biliary tree that characterizes PBC.


Fabrication of spatial modulated second order nonlinear structures and quasi-phase matched second harmonic generation in a poled azo-copolymer planar waveguide.
This work demonstrates that arbitrary types of spatially modulated second-order susceptibility (chi((2)) structures such as 1D and 2D, periodic and quasi-periodic structures can be obtained by using the combination of corona poling and direct laser writing (DLW) techniques. The fabrication technique is based on the photodepoling of azo-dye molecules caused by one-photon or two-photon absorption during the DLW process. Polarization and second harmonic generation (SHG) images of the fabricated structures were measured by electrostatic force microscope and SHG mapping techniques, respectively. Furthermore, quasi-phase-matched (QPM) enhanced SHG from a 1D periodically poled azo-copolymer planar waveguide is demonstrated using an optical parametric oscillator laser by scanning wavelength from 1500 to 1600 nm. The resonant wavelength of the QPM enhanced SHG is peaked at 1537 nm with FWHM is congruent to 2.5 nm.


The value of choice facilitates subsequent memory across development.
Both children and adults are more likely to remember information when they have control over their learning environment. Despite many demonstrations of this effect in the literature, it is still unclear how and why people are more likely to remember information that is obtained through their own actions rather than passively received. One possibility is that individuals are biased to remember the outcomes of their choices because doing so may often be beneficial. Having agency, or the ability to exert control, is valuable when individuals can act in an instrumental manner to achieve their goals. Preferentially encoding information encountered in such contexts may confer an advantage when making similar decisions in the future. However, it has not been directly examined whether modulating the value, or utility, of agency affects its mnemonic benefit. Additionally, the developmental trajectory of how the utility of agency affects memory is unclear. The current study examines whether the mnemonic benefit of agency is modulated by the utility of choice and whether this effect varies as a function of age. We tested 96 participants, ages 8 to 25, in a paradigm in which agency and its utility were separately manipulated at encoding. In contrast to previous studies, we did not find that simply having the ability to make a choice enhanced memory. Rather, when the utility of agency varied within the task, we only observed an agency-related memory benefit when the ability to choose had the greatest utility. This pattern was age-invariant, suggesting that this effect on memory is present in middle childhood and persists through adulthood.


Decagonal quasiferromagnetic microstructure on the penrose tiling.
The stable magnetization configurations of a ferromagnet on a quasiperiodic tiling have been derived theoretically. The magnetization configuration is investigated as a function of the ratio of the exchange to the dipolar energy. The exchange coupling is assumed to decrease exponentially with the distance between magnetic moments. It is demonstrated that for a weak exchange interaction the new structure, the quasiferromagnetic decagonal configuration, corresponds to the minimum of the free energy. The decagonal state represents a new class of frustrated systems where the degenerated ground state is aperiodic and consists of two parts: ordered decagon rings and disordered spin-glass-like phase inside the decagons.


Sodium intake reduction efforts in Lebanon.
Sodium intake reduction efforts in Lebanon are quite recent and have just started to take effect on the national level. Starting out from an academic institution, the Lebanese Action on Sodium and Health (LASH) campaign was established to counter the increasing prevalence of hypertension and associated adverse health effects. The campaign's strategy was based on four pillars: research, health communication, advocacy, and monitoring. The LASH group set out with determining: baseline sodium intake of the population, main sources of sodium intake, and the knowledge, attitudes, and behaviors (KAB) of the population as a situation analysis that prompts for action. This gave LASH tangible evidence of the magnitude of the problem and the need for the government, the food industry, and the consumers, to be mobilized to take part in devising a solution. Currently, Lebanon is at a stage of technically working to reduce the sodium content in the major sources of sodium, namely local bread and bread-like products. The next steps will include implementation of a plan for monitoring industry compliance, while studying other food targets, including dairy products and processed meat. Meanwhile, the health communication plan is ongoing and the Salt Awareness Week is celebrated every year with media appearances of LASH researchers to raise the issue to the public eye.


Microalbuminuria and cardiovascular risk.
Microalbuminuria is a marker for generalized vascular dysfunction. Its prevalence in United States and European general population surveys ranges from 6% to 10%. Increased risk for cardiovascular morbidity and mortality begins with albumin excretion rates that are well within normal limits. Although microalbuminuria interacts with the traditional cardiovascular risk factors, it has an independent relationship to renal and cardiovascular outcomes. For example, microalbuminuria doubles the risk for a cardiovascular event in patients with type 2 diabetes mellitus even after adjusting for the usual risk factors. Elevated rates of urinary albumin excretion predict target organ damage, notably renal disease, but are also related to left ventricular dysfunction, stroke, and myocardial infarction. Screening for microalbuminuria, which is recommended by several expert committees and associations, has become a readily accessible procedure. Screening can give clinicians prognostic information concerning cardiovascular risk and assist in guiding therapy. The goal of treatment is to prevent progression of, and even to reverse, microalbuminuria. Abundant evidence demonstrates that antihypertensive therapy is an important key to the control of urinary albumin excretion, and blockade of the renin-angiotensin system (with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers) is the treatment of choice. These drugs have successfully halted or delayed the progression to nephropathy and have reversed elevated rates of albumin excretion to normal values, even when blood pressure reduction has been minimal.


Three new temperate phages of Bacillus subtilis.
Three temperate bacteriophages of Bacillus subtilis were isolated from soil samples and analysed, together with all the other known temperate phages of this organism, with respect to their host range, immunity, serology and DNA restriction pattern, and by other tests. The results show that the newly isolated phages are new members of the immunity sub-group I of the group III of B. subtilis temperate bacteriophages. We named these new phages IG1, IG3 and IG4.


Isolation and characterization of endothelial progenitor cells from human blood.
Circulating endothelial progenitor cells (EPCs) in adult human peripheral blood were originally identified in 1997 by Asahara et al., which challenged the paradigm that vasculogenesis is a process restricted to embryonic development. Since their original identification, EPCs have been extensively studied as biomarkers to assess the risk of cardiovascular disease in human subjects and as a potential cell therapeutic for vascular regeneration. Endothelial colony-forming cells (ECFCs), which are a subtype of EPCs, were recently identified from circulating adult and human umbilical cord blood. In contrast to other types of EPCs, which display various monocyte/macrophage phenotypes and functions, ECFCs are characterized by robust proliferative potential, secondary and tertiary colony formation upon replating, and de novo blood vessel formation in vivo when transplanted into immunodeficient mice. In this unit, we describe detailed methodologies for isolation and characterization of ECFCs from both human peripheral and umbilical cord blood.


Pax6 is a key component of regulated glucagon secretion.
The Pax6 transcription factor is crucial for pancreatic α-cells. Indeed, Pax6-deficient mouse models are characterized by markedly altered α-cell differentiation. Our objective was to investigate the role of Pax6 in glucagon secretion process. We used a Pax6-deficient model in rat primary enriched-α cells with specific small interfering RNA leading to a 70% knockdown of Pax6 expression. We first showed that Pax6 knockdown decreases glucagon biosynthesis as well as glucagon release. Through physiological assays, we demonstrated that the decrease of Pax6 affects specifically acute glucagon secretion in primary α-cell in response to glucose, palmitate, and glucose-dependent insulinotropic peptide (GIP) but not the response to arginine and epinephrine. We identified in Pax6 knockdown model that genes involved in glucagon secretion such as the glucokinase (GCK), G protein-coupled receptor (GPR40), and GIP receptor (GIPR) as well as the corresponding proteins were significantly decreased whereas the insulin receptor (IR) Kir6.2/Sur1, and glucose transporter 1 genes were not affected. We demonstrated that Pax6 directly binds and activates specific elements on the promoter region of the GPR40, GCK, and GIPR genes. Finally, through site-directed mutagenesis experiments, we showed that disruption of Pax6 binding on the GCK, GPR40, and GIPR gene promoters led to specific decreases of their activities in the αTC1.9 glucagon-producing cell line. Hence our results indicate that Pax6 acts on the regulation of glucagon secretion at least through the transcriptional control of GCK, GPR40, and GIPR. We propose that Pax6 is not only critical for glucagon biosynthesis but also for glucagon secretion particularly in response to nutrients.


[Gluco-incretin hormones in insulin secretion and diabetes].
Nutrient ingestion triggers a complex hormonal response aimed at stimulating glucose utilization in liver, muscle and adipose tissue to minimize the raise in blood glucose levels. Insulin secretion by pancreatic beta cells plays a major role in this response. Although the beta cell secretory response is mainly controlled by blood glucose levels, gut hormones secreted in response to food intake have an important role in potentiating glucose-stimulated insulin secretion. These gluco-incretin hormones are GLP-1 (glucagon-like peptide-1) and GIP (gluco-dependent insulinotropic polypeptide). Their action on pancreatic beta cells depends on binding to specific G-coupled receptors linked to activation of the adenylyl cyclase pathway. In addition to their effect on insulin secretion both hormones also stimulate insulin production at the transcriptional and translational level and positively regulate beta cell mass. Because the glucose-dependent insulinotropic action of GLP-1 is preserved in type 2 diabetic patients, this peptide is now developed as a novel therapeutic drug for this disease.


Differences in survival between colon and rectal cancer from SEER data.
Little is known about colorectal cancer or colon and rectal cancer. Are they the same disease or different diseases? The aim of this epidemiology study was to compare the features of colon and rectal cancer by using recent national cancer surveillance data. Data included colorectal cancer (1995-2008) from the Surveillance, Epidemiology, and End Results Program (SEER) database. Only adenocarcinoma was included for analysis. A total of 372,130 patients with a median follow-up of 32 months were analyzed. Mean survival of patients with the same stage of colon and rectal cancer was evaluated. Around 35% of patients had stage information. Among them, colon cancer patients had better survival than those with rectal cancer, by a margin of 4 months in stage IIB. In stage IIIC and stage IV, rectal cancer patients had better survival than colon cancer patients, by about 3 months. Stage IIB colorectal cancer patients had a poorer prognosis than those with stage IIIA and IIIB colorectal cancer. After adjustment of age, sex and race, colon cancer patients had better survival than rectal cancer of stage IIB, but in stage IIIC and IV, rectal cancer patients had better survival than colon cancer. The study is limited by its retrospective nature. This was a population-based study. The prognosis of rectal cancer was not worse than that of colon cancer. Local advanced colorectal cancer had a poorer prognosis than local regional lymph node metastasis. Stage IIB might require more aggressive chemotherapy, and no less than that for stage III.


Disruption of vector transmission by a plant-expressed viral glycoprotein.
Vector-borne viruses are a threat to human, animal, and plant health worldwide, requiring the development of novel strategies for their control. Tomato spotted wilt virus (TSWV) is one of the 10 most economically significant plant viruses and, together with other tospoviruses, is a threat to global food security. TSWV is transmitted by thrips, including the western flower thrips, Frankliniella occidentalis. Previously, we demonstrated that the TSWV glycoprotein GN binds to thrips vector midguts. We report here the development of transgenic plants that interfere with TSWV acquisition and transmission by the insect vector. Tomato plants expressing GN-S protein supported virus accumulation and symptom expression comparable with nontransgenic plants. However, virus titers in larval insects exposed to the infected transgenic plants were three-log lower than insects exposed to infected nontransgenic control plants. The negative effect of the GN-S transgenics on insect virus titers persisted to adulthood, as shown by four-log lower virus titers in adults and an average reduction of 87% in transmission efficiencies. These results demonstrate that an initial reduction in virus infection of the insect can result in a significant decrease in virus titer and transmission over the lifespan of the vector, supportive of a dose-dependent relationship in the virus-vector interaction. These findings demonstrate that plant expression of a viral protein can be an effective way to block virus transmission by insect vectors.


Aspirator modification for the removal of mosquitoes from tight spaces.
An insect aspirator was modified to remove mosquitoes that entered an animal-baited experimental cage within a cage. The modified aspirator is easy to maneuver inside tight spaces, powerful enough to aspirate mosquitoes but not remove scales or fluorescent marking powders, and will run continuously for at least 45 min.


Anxiety and executive functions in mid-to-late life: the moderating role of sleep.
Objectives: The goal of the study was to examine the influence of sleep efficiency on the relationship between anxiety and executive functions.Method: Secondary data analyses of 82 community-dwelling middle-aged and older adults were performed (M age = 63.00, SD = 8.64). Anxiety was measured using the trait anxiety subscale of the State-Trait Anxiety Inventory. Sleep efficiency was measured using one-week of sleep diary data. Two executive functions, cognitive flexibility and inductive reasoning, were measured using the Trail-Making Test and Letter Series task, respectively. SPSS PROCESS macro software version 2 was used to assess the moderating role of sleep efficiency in the relationship between anxiety and executive functions.Results: Sleep significantly moderated the relationship between anxiety and inductive reasoning. Among middle-aged and older adults with high anxiety, those with good sleep efficiency displayed significantly better inductive reasoning than those with poor sleep efficiency after controlling for age, gender, and education (ΔR2 = .05, p = .017). Sleep efficiency did not significantly moderate the relationship between anxiety and cognitive flexibility.Conclusion: Sleep efficiency weakened the association between anxiety and inductive reasoning in middle-aged and older adults. Evidence from the study suggests better sleep may limit the negative effects of anxiety on executive functions in mid-to-late life. Further research is needed to elucidate the impact of anxiety and sleep on executive functions in clinical populations with anxiety.