Accuracy of PET for diagnosis of solid pulmonary lesions with 18F-FDG uptake below the standardized uptake value of 2.5.
Benign and malignant pulmonary lesions usually are differentiated by 18F-FDG PET with a semiquantitative 18F-FDG standardized uptake value (SUV) of 2.5. However, the frequency of malignancies with an SUV of <2.5 is significant, and pulmonary nodules with low 18F-FDG uptake often present diagnostic challenges. Among 360 consecutive patients who underwent 18F-FDG PET to evaluate pulmonary nodules found on CT, we retrospectively analyzed 43 who had solid pulmonary lesions (excluding lesions with ground-glass opacity, infiltration, or benign calcification) with an SUV of <2.5. The uptake of 18F-FDG was graded by a visual method (absent, faint, moderate, or intense) and 2 semiquantitative methods (SUV and contrast ratio [CR]). Final classification was based on histopathologic findings or at least 6 mo of clinical follow-up. We found 16 malignant (diameter, 8-32 mm) and 27 benign (7-36 mm) lesions. When faint visual uptake was the cutoff for positive 18F-FDG PET results, the receiver-operating-characteristic (ROC) analysis correctly identified all 16 malignancies and yielded false-positive results for 10 of 27 benign lesions. Sensitivity was 100%, specificity was 63%, and the positive and negative predictive values were 62% and 100%, respectively. When an SUV of 1.59 was the cutoff for positive 18F-FDG PET results, the ROC analysis revealed 81% sensitivity, 85% specificity, and positive and negative predictive values of 77% and 89%, respectively. At a cutoff for positive 18F-FDG PET results of a CR of 0.29, the ROC analysis revealed 75% sensitivity, 82% specificity, and positive and negative predictive values of 71% and 85%, respectively. The areas under the curve in ROC analyses did not differ significantly among the 3 analyses (visual, 0.84; SUV, 0.81; and CR, 0.82). Analyses of intra- and interobserver variabilities indicated that visual and SUV analyses were quite reproducible, whereas CR analysis was poorly reproducible. These results suggested that for solid pulmonary lesions with low 18F-FDG uptake, semiquantitative approaches do not improve the accuracy of 18F-FDG PET over that obtained with visual analysis. Pulmonary lesions with visually absent uptake indicate that the probability of malignancies is very low. In contrast, the probability of malignancy in any visually evident lesion is about 60%.


Uptake of provider initiated HIV counseling and testing (PICT) among out patient department (OPD) clients with possible clinical signs of HIV infection in Addis Ababa.
Developments have been seen in recent years in global efforts to address the AIDS epidemnic. HIV counseling and testing (VCT) is the key entry point to prevention, care, treatment and support services. To improve the slow uptake besides VCT different alternatives have been proposed, namely provider-initiated HIV counseling and testing (PICT). To assess uptake of provider initiated HIV counseling and testing among out patient department (OPD) clients with possible clinical signs of HIV infection and factors associated with it. Facility based cross sectional study was conducted on 423 OPD clients with possible clinical signs of HIV infection in 12 government health centers in Addis Ababa. Once the health facilities were selected randomly from each sub cities, study subjects who came to the health centers were interviewed consecutively. The pre-test and post-test acceptability rates among those who showed willingness to PICT, were 0.98 and 0.96 respectively where as the overall acceptability rate of all study participants was 0.67. Compared with age group 15-24, subjects 25-34 years old have higher rate of willingness (Adj.OR = 8.98, 95% CI = 1.2-66.5) and acceptability (Adj.OR = 6.4 CI = 1.2-33.6). On the other hand those who had "less" support for PITC were less likely to be willing (AOR = 0.03; CI = 0.002-0.43) and accept the test (AOR = 0.02; 95% CI = 0.02-0.3) than who supported it "extremely". Though knowledge about PICT among the study subjects was not satisfactory the relatively high willingness and acceptability identified in this study is promising for wider application towards strengthened prevention and control of HIV/AIDS. We recommend that PICT needs to be implemented at all levels of health facilities in Ethiopia.


Suicidality among South Brazilian tobacco growers.
To assess prevalence of suicidal ideation and suicide attempt among South Brazilian tobacco growers and to analyze the associated factors related to the suicidal ideation. A cross-sectional study was conducted in 2011 with a random sample of 2469 tobacco growers in São Lourenço do Sul/RS. Suicidal ideation was characterized by the question "Has the thought of ending your life been on your mind?". Suicide attempt was assessed by the question "Have you ever tried to kill yourself?". Investigation of factors associated with suicidal ideation was done by means of Poisson regression. Prevalence of suicidal ideation and suicide attempt was 2.5 % and 1.2 % respectively. In the adjusted analysis, suicidal ideation was associated with being female, older age, moderate participation in religious activities and difficulty in paying debts. Those who worked in activities that required inadequate postures (hunched over or other forced positions), as well as farmers who performed 6-9 pesticide-related tasks demonstrated greater risk of suicidal ideation. Regarding health conditions, medical diagnosis of asthma, chronic low back pain, number of lifetime green tobacco sickness episodes and lifetime pesticide poisoning were positively associated with suicidal ideation. Suicidal thoughts and attempts are relevant mental health problems among tobacco growers. Reducing pesticide use, as well as exposure to nicotine and improving socio-economic conditions, can reduce suicidal ideation and improve the mental health of exposed workers.


HPV test results and histological follow-up results of patients with LSIL Cervical Cytology from the Largest CAP-certified laboratory in China.
Age-adjusted evaluations have explored the possible utility of (HPV test results in women with LSIL Pap. We investigated HPV test results and histopathologic follow-up results of LSIL patients from China's largest CAP-certified laboratory. Patients with LSIL between 2011 and 2015 from the Guangzhou Kingmed Diagnostics were retrospectively retrieved and their hrHPV test results and histological follow-up results were collected and analyzed. LSIL result was identified in 37,895 cases from 2,206,588 Pap tests (1.7%) including 1,513,265 liquid-based cytology and 693,323 conventional Pap tests. The average of these women was 38.4 years (15-88). The LSIL reporting rate in women <30 years was significantly higher than that in women > 30 years (2.1% vs 1.7%). The age specific reporting LSIL rates declined with increased age. 8,014 of 37,895 (21.2%) women with LSIL cytology also had HC2 HPV test results. 75.8% of women with LSIL Pap tests were hrHPV+ and the HPV+ rates declined with increased age except in patients older than 60 years. Overall histopathologic diagnoses within 6 months after LSIL were identified in 5,987 of 37,895 patients at Guangzhou Kingmed Diagnostics. CIN2/3 was identified in 15.2% patients, CIN1 in 66.9%, negative in 14.9% patients. No invasive carcinoma was found in all patients. Of 8014 patients with LSIL Pap test and HPV testing results, 1727 patients had histological follow-up within 6 months after Pap cytology test and HPV testing. The detection rate of CIN2/3 was significantly higher in patients with positive HPV testing result than that in patients with negative HPV testing result (17.8% vs. 8.1%). Among patients with LSIL/HPV negative tests, CIN2/3 was detected in 1 of 30 (3.3%) women aged 50 years and above, appearing lower than those in women less than 50 years (8.0%, 28/351, P=0.357). This is the largest histological follow-up study in women with LSIL Pap from China and the data are helpful in establishing a baseline for better understanding the status of cervical screening in China. The 85.1% positive predict value of LSIL Pap cytology for follow-up CIN lesion was within currently recognized benchmark ranges.


BNT162b2 Covid-19 vaccine does not affect fertility as explored in a pilot study of women undergoing IVF treatment.
The COVID-19 pandemic spreads worldwide, causing devastating consequences. BioNTech and Pfizer's BNT162b2 vaccine was one of the first vaccines to receive emergency-use authorization. However, its impact on women's fertility has not been primarily assessed leading to spread of unfounded rumors, causing vaccine hesitancy. We investigate the possible impact of BNT162b2 COVID-19 vaccine on in vitro fertilization (IVF) outcomes. We compared data from 42 women undergoing their first IVF following 2 doses of BNT162b2 vaccination to 42 unvaccinated women undergoing their first IVF. The first outcome consisted of the pregnancy based on first hCG value; secondary outcomes were IVF cycle outcomes. A second analysis was done on 29 paired patients from both groups based on age, FSH, and the indication for IVF. We report different levels of the pregnancy formation; oocyte's development: numbers of oocytes retrieved (9.3±6.8 vs. 11.5 ± 7.9, p=0.19) and matured (6.9±4.8 vs. 9.1 ± 6.6, p=0.14), and embryonal stage: fertilization rates (64.1±26.6 vs. 66.3±23.3, p=0.14), the quantity (4.3 ± 3.2 vs. 5.7±4.4, p=0.23) and qualities of embryos (good/fair/poor) at day 3 were comparable. The analysis showed no significant difference between the groups, and the odds for pregnancy were similar (OR=0.9, 95% CL[0.3-2.8] p.value 0.833). From our results, this vaccine does not affect IVF performance and outcomes from the early stage of oocyte development through to the early beginning of pregnancy; therefore, it seems that the BNT162b2 vaccine does not compromise women's fertility.


Zwitterionic self-assembly of L-methionine nanogratings on the Ag(111) surface.
The engineering of complex architectures from functional molecules on surfaces provides new pathways to control matter at the nanoscale. In this article, we present a combined study addressing the self-assembly of the amino acid L-methionine on Ag(111). Scanning tunneling microscopy data reveal spontaneous ordering in extended molecular chains oriented along high-symmetry substrate directions. At intermediate coverages, regular biomolecular gratings evolve whose periodicity can be tuned at the nanometer scale by varying the methionine surface concentration. Their characteristics and stability were confirmed by helium atomic scattering. X-ray photoemission spectroscopy and high-resolution scanning tunneling microscopy data reveal that the L-methionine chaining is mediated by zwitterionic coupling, accounting for both lateral links and molecular dimerization. This methionine molecular recognition scheme is reminiscent of sheet structures in amino acid crystals and was corroborated by molecular mechanics calculations. Our findings suggest that zwitterionic assembly of amino acids represents a general construction motif to achieve biomolecular nanoarchitectures on surfaces.


A Predictive Model of Postnatal Surgical Intervention in Children With Prenatally Detected Congenital Anomalies of the Kidney and Urinary Tract.
The aim of this study was to identify predictive factors and develop a model to assess individualized risk of postnatal surgical intervention in patients with antenatal hydronephrosis. This is a retrospective cohort study of 694 infants with prenatally detected congenital anomalies of kidney and urinary tract with a median follow-up time of 37 months. The main event of interest was postnatal surgical intervention. A predictive model was developed using Cox model with internal validation by bootstrap technique. Of 694 patients, 164 (24%) infants underwent surgical intervention in a median age of 7.8 months. Predictors of the surgical intervention in the model were: baseline glomerular filtration rate, associated hydronephrosis, presence of renal damage and the severity of renal pelvic dilatation. The optimism corrected c statistic for the model was 0.84 (95%CI, 0.82-0.87). The predictive model may contribute to identify infants at high risk for surgical intervention. Further studies are necessary to validate the model in patients from other settings.


Bacteria engineered with intracellular and extracellular nanomaterials for hierarchical modulation of antitumor immune responses.
Induction of immunogenic cell death (ICD) by hyperthermia can initiate adaptive immune responses, emerging as an attractive strategy for tumor immunotherapy. However, ICD can induce proinflammatory factor interferon-γ (IFN-γ) production, leading to indoleamine 2,3-dioxygenase 1 (IDO-1) activation and an immunosuppressive tumor microenvironment, which dramatically reduces the ICD-triggered immunotherapeutic efficacy. Herein, we developed a bacteria-nanomaterial hybrid system (CuSVNP20009NB) to systematically modulate the tumor immune microenvironment and improve tumor immunotherapy. Attenuated Salmonella typhimurium (VNP20009) that can chemotactically migrate to the hypoxic area of the tumor and repolarize tumor-associated macrophages (TAMs) was employed to intracellularly biosynthesize copper sulfide nanomaterials (CuS NMs) and extracellularly hitchhike NLG919-embedded and glutathione (GSH)-responsive albumin nanoparticles (NB NPs), forming CuSVNP20009NB. After intravenous injection into B16F1 tumor-bearing mice, CuSVNP20009NB could accumulate in tumor tissues and repolarize TAMs from the immunosuppressive M2 to immunostimulatory M1 phenotype and release NLG919 from extracellular NB NPs to inhibit IDO-1 activity. Under further near infrared laser irradiation, intracellular CuS NMs of CuSVNP20009NB could photothermally induce ICD including calreticulin (CRT) expression and high mobility group box 1 (HMGB-1) release, promoting intratumoral infiltration of cytotoxic T lymphocytes. Finally, CuSVNP20009NB with excellent biocompatibility could systematically augment immune responses and significantly inhibit tumor growth, holding great promise for tumor therapy.


Abundance, diversity and domain architecture variability in prokaryotic DNA-binding transcription factors.
Gene regulation at the transcriptional level is a central process in all organisms, and DNA-binding transcription factors, known as TFs, play a fundamental role. This class of proteins usually binds at specific DNA sequences, activating or repressing gene expression. In general, TFs are composed of two domains: the DNA-binding domain (DBD) and an extra domain, which in this work we have named "companion domain" (CD). This latter could be involved in one or more functions such as ligand binding, protein-protein interactions or even with enzymatic activity. In contrast to DBDs, which have been widely characterized both experimentally and bioinformatically, information on the abundance, distribution, variability and possible role of the CDs is scarce. Here, we investigated these issues associated with the domain architectures of TFs in prokaryotic genomes. To this end, 19 families of TFs in 761 non-redundant bacterial and archaeal genomes were evaluated. In this regard we found four main groups based on the abundance and distribution in the analyzed genomes: i) LysR and TetR/AcrR; ii) AraC/XylS, SinR, and others; iii) Lrp, Fis, ArsR, and others; and iv) a group that included only two families, ArgR and BirA. Based on a classification of the organisms according to the life-styles, a major abundance of regulatory families in free-living organisms, in contrast with pathogenic, extremophilic or intracellular organisms, was identified. Finally, the protein architecture diversity associated to the 19 families considering a weight score for domain promiscuity evidenced which regulatory families were characterized by either a large diversity of CDs, here named as "promiscuous" families given the elevated number of variable domains found in those TFs, or a low diversity of CDs. Altogether this information helped us to understand the diversity and distribution of the 19 Prokaryotes TF families. Moreover, initial steps were taken to comprehend the variability of the extra domain in those TFs, which eventually might assist in evolutionary and functional studies.


Characterization of shade avoidance responses in Lotus japonicus.
Sessile plants must continuously adjust their growth and development to optimize photosynthetic activity under ever-fluctuating light conditions. Among such light responses in plants, one of the best-characterized events is the so-called shade avoidance, for which a low ratio of the red (R):far-red (FR) light intensities is the most prominent stimulus. Such shade avoidance responses enable plants to overtop their neighbors, thereby enhancing fitness and competitiveness in their natural habitat. Considerable progress has been achieved during the last decade in understanding the molecular mechanisms underlying the shade avoidance responses in the model rosette plant, Arabidopsis thaliana. We characterize here the fundamental aspects of the shade avoidance responses in the model legume, Lotus japonicus, based on the fact that its phyllotaxis (or morphological architecture) is quite different from that of A. thaliana. It was found that L. japonicus displays the characteristic shade avoidance syndrome (SAS) under defined laboratory conditions (a low R:FR ratio, low light intensity, and low blue light intensity) that mimic the natural canopy. In particular, the outgrowth of axillary buds (i.e., both aerial and cotyledonary shoot branching) was severely inhibited in L. japonicus grown in the shade. These results are discussed with special emphasis on the unique aspects of SAS observed with this legume.


The papez circuit in first-episode, treatment-naive adults with major depressive disorder: combined atlas-based tract-specific quantification analysis and voxel-based analysis.
Previous findings suggest that the Papez Circuit may have a role in major depressive disorders. We used atlas-based tract-specific quantification analysis and voxel-based analysis to examine the integrity of white matter tracts involved in mood regulation (including tracts in the Papez Circuit). Diffusion tensor imaging acquired from 35 first-episode, treatment-naive adults with major depressive disorders and 34 healthy adult controls were compared. Our statistical approach compared structural integrity of 11 major white matter tracts between the major depressive disorder and adult controls, as well as illness duration influence in patients. Fractional anisotropy was decreased in the hippocampal cingulum and in the anterior thalamic radiation according to both analytical approaches, all of which were important tracts included in the Papez Circuit. Our results support the role of the Papez Circuit in major depressive disorders with the minimal probability of false positive due to similar findings in both analyses that have complementary advantages. Dysfunction of the Papez Circuit may be a potential marker for studying the pathogenesis of major depressive disorders.


Human pharmacokinetics and safety profile of finafloxacin, a new fluoroquinolone antibiotic, in healthy volunteers.
Finafloxacin is a new fluoroquinolone antibiotic with the unique property of increasing antibacterial activity at pH values lower than neutral. Whereas its antibacterial activity at neutral pH matches that of other quinolones in clinical use, it is expected to surpass this activity in tissues and body fluids acidified by the infection or inflammation processes. Pharmacokinetic parameters of oral single and multiple doses of up to 800 mg of finafloxacin and safety/tolerability observations were assessed in a phase I study including 95 healthy volunteers. Finafloxacin is well absorbed after oral administration, generating maximum concentrations (C(max)s) in plasma at least comparable to those of other fluoroquinolones, with a half-life of around 10 h. About one-third of the dose is excreted unchanged in the urine. Renal elimination appears to be a saturable process leading to slight increases of the area under the concentration-time curve extrapolated to infinity and dose normalized (AUC(∞,norm)) at dosages of 400 mg and above. Safety and tolerability data characterize finafloxacin as a drug with a favorable safety profile. In particular, adverse reactions regarded as class-typical of fluoroquinolones, such as, e.g., electrocardiogram (ECG) changes, neurotoxic effects, or hypoglycemia, were not observed in the study population.


Spiropyran-Isoquinoline Dyad as a Dual Chemosensor for Co(II) and In(III) Detection.
Spiropyran derivatives have been studied as light-regulated chemosensors for a variety of metal cations and anions, but there is little research on chemosensors that simultaneously detect multiple metal cations. In this study, a spiropyran derivative with isoquinoline, SP-IQ, was prepared and it functions investigated as a light-regulated sensor for both Co2+ and In3+ cations. A colorless nonfluorescent SP-IQ converts to a pink-colored fluorescent MC-IQ by UV irradiation or standing in the dark, and MC-IQ returns to SP-IQ with visible light. Upon UV irradiation with the Co2+ cation for 7 min, the stronger absorption at 540 nm and the similar fluorescence intensity at 640 nm are observed, compared to when no metal cation is added, due to the formation of a Co2+ complex with pink color and pink fluorescence. When placed in the dark with the In3+ cation for 7 h, the colorless solution of SP-IQ changes to the In3+ complex with yellow color and pink fluorescence, which shows strong absorption at 410 nm and strong fluorescence at 640 nm. Selective detection of the Co2+ cation with UV irradiation and the In3+ cation in the dark could be possible with SP-IQ by both absorption and fluorescence spectroscopy or by the naked eye.


Chromogranin A in the human gastrointestinal tract: an immunocytochemical study with region-specific antibodies.
We studied the immunoreactivity of 12 different region-specific antibodies to the chromogranin A (CgA) molecule in the various neuroendocrine cell types of the human gastrointestinal (GI) tract by using double immunofluorescence techniques. These staining results were compared with others obtained with a commercial monoclonal CgA antibody (LK2H10). G (gastrin)-cells showed immunoreactivity to virtually all region-specific antibodies, but with varying frequency. Most intestinal EC (enterochromaffin)- and L (enteroglucagon)-cells were immunoreactive to the antibodies to the N-terminal and mid-portion of the CgA molecule, whereas the EC-cells in the stomach reacted with fewer region-specific antibodies. D (somatostatin)-cells reacted to the CgA 411-424 antibody and only occasionally showed immunoreactivity to the other CgA antibodies. A larger cytoplasmic area was stained with the antibodies to CgA 17-38 and 176-195 than with the other antibodies tested. These differences in staining pattern may reflect different cleavage of the CgA molecule in different cell types and at different regions of the GI tract.


[Screening using Krypto-Haem-SSWR for the early detection of colorectal carcinomas and adenomas].
In the last 30 years, colorectal carcinomas have been stated to occur markedly in all industrial countries. From colonic and rectal malignant tumors, the amounts of 4225 in 1961 and 7220 in 1984 were newly registered in GDR. Thus the number of patients with colorectal carcinomas showed the decrease for up to 70.9% starting from 1961. The biochemical Krypto-Haem-SSWR screening test has been implemented during the last few years by members of proctologic section. Colorectal carcinoma was stated in 48 asymptomatic subjects aged more than 45 years, and colonic adenoma in 83, respectively. At present, the yearly screening of occult bleeding into faeces is the unique measure contributing to early recognition of colorectal carcinomas and precancerous lesions.


[Importance of coloncontrast enema].
Screening for colorectal cancer starts with digital exploration of the rectum and was extended in 1977 using the haemoccult test. It was referred to detect 24% of malignancies, but with a high number of false positive findings. Combination of regular follow up examinations and coloscopy reached a sensitivity of 80%. International studies demonstrated the need of a complete colon examination, so that the coloscopy is actually an important screening method in Germany. The coloncontrast examination is a safe, cost-effective method with a low complication rate. It is suitable especially for patients, in which the colonoscopic evaluation of the colon was not complete and provides additional morphological informations in many cases.


Proton MR spectroscopy of Wernicke encephalopathy.
Two patients with acute thiamine deficiency were examined with thalamic single-voxel proton MR spectroscopy. T2-weighted images exhibited increased signal intensity. N-acetylaspartate (NAA)/creatine (Cr) ratios were low without detectable lactate. Owing to substantially decreased choline (Cho) T2, the Cho/Cr ratio was not decreased. After thiamine therapy, the NAA/Cr ratio increased, paralleling clinical improvement and reduction in the areas of signal-intensity changes.


Patient, Caregiver, and Oncologist Experiences With and Perceptions of Racial Bias and Discrimination in Cancer Care Delivery.
Cancer prevention and treatment systems are significantly impacted by interpersonal, organizational, and structural and systemic racism. A wide body of research has found that racial disparities in access to guideline-adherent cancer care are pervasive throughout the United States and contributing factors include social determinants of health, insurance status, and bias and discrimination in care delivery. Although the existence of racial disparities in cancer care and outcomes is well established, there has been limited research exploring the patient and caregiver experience with bias and discrimination in cancer care. Two national surveys were conducted, one of patients and caregivers and one of oncologists. The surveys examined patient and caregiver experiences with and oncologist perceptions of racial disparities in cancer care. The surveys found that when patients and caregivers were asked about negative care experiences, differences across race were observed. Patients and caregivers identifying as African American/Black (AA/B) or Hispanic/Latino (H/L) were more likely to report at least one negative care experience than patients and caregivers identifying as White (W). Patients who were AA/B or H/L were also more likely than W patients to report that the healthcare system treats people unfairly based on their racial or ethnic background and that racial bias occurs often or very often when a patient and doctor are of different racial/ethnic background. A slight majority of oncologists reported that the healthcare system treats people unfairly based on their racial or ethnic background. The survey results highlight a need for improved racial representation in the oncology professional workforce, improved implicit bias training, and improved clinical trial recruitment efforts.


DNA Nanofirecrackers Assembled through Hybridization Chain Reaction for Ultrasensitive SERS Immunoassay of Prostate Specific Antigen.
Isothermal nucleic acid amplification technology has been widely adopted for analytical chemistry with the purpose of sensitivity improvement. Herein we present an ultrasensitive concatenated hybridization chain reaction (C-HCR) based surface-enhanced Raman scattering (SERS) immunoassay by forming antibody-antigen-aptamer heterosandwich structures with the model analyte of total prostate specific antigens (tPSA). In the C-HCR, two HCRs, one proceeds with two hairpins and the other with four biotin-modified hairpins, are coupled, making the formation of DNA nanofirecrackers with the lengths longer than 200 nm and more than four hundred million binding sites of streptavidin modified enzymes. These types of DNA nanofirecrackers through the aptamer encoded linker strand to form heterosandwich structures could provide a general signal application platform such as enzyme catalysis with high amplification efficiency. As a proof of concept, the Au@Ag core-shell nanostructure based SERS immunoassay with excellent signal amplification has been developed by employing the streptavidin modified alkaline phosphatase (SA-ALP) through its catalysis of 2-phospho-l-ascorbic acid trisodium salt (AAP) to form Au@Ag core-shell nanostructures via the formation of ascorbic acid (AA) to reduce AgNO3 and deposition of silver element on gold nanorods (AuNRs). The newly developed method has a detection limit as low as 0.94 fg/mL and has successfully achieved the detection of serum samples from clinical patients, which was consistent with the clinical test results, showing that this C-HCR strategy to form DNA nanofirecrackers has great potential in clinical applications.


Development of an Experimental Ex Vivo Wound Model to Evaluate Antimicrobial Efficacy of Topical Formulations.
Wound infections are considered a major cause for wound-associated morbidity. There is a high demand for alternative, robust, and affordable methods that can provide relatable and reproducible results when testing topical treatments, both in research and in the pharmaceutical industry. Here we present an ex vivo wound infection model using porcine skin and a burn wounding method, allowing for the efficacy evaluation of topical antimicrobial formulations. Utilizing this model, we demonstrate the potential of topical treatments after infecting the wounds with clinically significant bacteria, P. aeruginosa and S. aureus. We show that the method is compatible with several analytical tools used to analyze infection and antimicrobial effects. Both bacterial strains successfully infected the wound surface, as well as deeper regions of the tissue. Quantification of viable bacteria on the wound surface and in the tissue, longitudinal measurements of bioluminescence, fluorescence microscopy, and scanning electron microscopy were used to confirm the effects of antibacterial treatments. Furthermore, we show that biofilms are formed on the wound surface, indicating that the demonstrated method mirrors typical in vivo infections.


Cross-cultural adaptation and validation of the Italian version of the Montreal Children's Hospital Feeding Scale in a special healthcare needs population.
The Montreal Children's Hospital Feeding Scale (MCH-FS) allows paediatricians and other health care professionals to identify feeding difficulties among children. To translate and adapt the MCH-FS into Italian, and to evaluate the validity and reliability of this Italian version of the Montreal Children's Hospital Feeding Scale (I-MCH-FS). A total of 150 children with special healthcare needs were admitted to the Rare Disease Unit of the Paediatrics Department at the Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy, between March 2021 and March 2022 (74 males; mean age = 3.85 ± 1.96 years; median age = 4 years; age range = 6 months-6 years and 11 months) and 150 healthy participants (83 males; mean age = 3.5 ± 1.98 years; median age = 3 years; age range = 6 months-6 years and 11 months) were included in the study, which was approved by the local ethics committee. The original version of the MCH-FS was translated and cross-cultural adapted through five stages: (1) initial translation, (2) synthesis of the translations, (3) back translation, (4) expert committee and (5) test of the prefinal version. Test-retest reliability and internal consistency were assessed using Pearson r, Spearman r and Cronbach's alpha, respectively. Construct validity was established by comparing data obtained from patients with those of healthy participants using the Mann-Whitney U-test. A Pearson r of 0.98, a Spearman r of 0.95 and Cronbach's alpha value of 0.86 were obtained. In the clinical group, 40.6% children were classified as having feeding disorders (n = 61), while in the normative group 4.7% were diagnosed with feeding problems (n = 7). Mean total score of the clinical group was significatively different from the normative's. The I-MCH-FS is a valid and reliable one-page, quick screening tool used to identify feeding disorders among children with special needs in outpatient paediatric setting. What is already known on the subject The MCH-FS is a valid and reliable parent-report measure aimed at discriminating between children presenting or not feeding disorders. What this paper adds to existing knowledge This paper presents the translation and cross-cultural adaptation of the scale into the Italian language. What are the potential or actual clinical implications of this work? The Italian version of the MCH-FS can be used in the special healthcare needs population.


Computational investigation of hemodynamics in hardshell venous reservoirs: A comparative study.
Extracorporeal circulation using heart-lung-machines is associated with a profound activation of corpuscular and plasmatic components of circulating blood, which can also lead to deleterious events such as systemic inflammatory response and hemolysis. Individual components used to install the extracorporeal circulation have an impact on the level of activation, most predominantly membrane oxygenators and hardshell venous reservoirs as used in extracorporeal systems. The blood flows in two different hardshell reservoirs are computationally investigated. A special emphasis is placed on the prediction of an onset of transition and turbulence generation. Reynolds-averaged numerical simulations (RANS) based on a transitional turbulence model, as well as large eddy simulations (LES) are applied to achieve an accurate prediction. In the LES analysis, the non-Newtonian behavior of the blood is considered via the Carreau model. Blood damage potential is quantified applying the Modified Index of Hemolysis (MIH) based on the predicted flow fields. The results indicate that the flows in both reservoirs remain predominantly laminar. For one of the reservoirs, considerable turbulence generation is observed near the exit site, caused by the specific design for the connection with the drainage tube. This difference causes the MIH of this reservoir to be nearly twice as large as compared to the alternative design. However, a substantial improvement of these performance criteria can be expected by a local geometry modification.


CT and MR imaging findings of non-neoplastic cystic lesions of the parotid gland.
A variety of neoplastic and non-neoplastic lesions of the parotid gland can present with a predominantly cystic architecture, and although radiologists frequently encounter cystic parotid tumors, other non-neoplastic lesions should also be included in the differential diagnoses of cystic parotid lesions. Non-neoplastic cystic lesions are usually classified as either congenital/acquired cystic lesions or inflammatory/infectious lesions. Adequate knowledge about these rare conditions is essential for appropriate diagnosis and optimal treatment strategy. This review article describes CT and MR imaging features of non-neoplastic cystic lesions of the parotid gland and provides helpful suggestions on the differential diagnoses for cystic parotid lesions.


Comparative Quality Control Study of Different Brands of Diclofenac Sodium Tablet Available in Local and Government Pharmacies by In-Vitro Testing.
The objective of this study is to conduct in-vitro quality control testing of diclofenac sodium tablets involves weight variation test, drug assay, friability test, and the disintegration and dissolution test. Two brands of diclofenac sodium tablets were used in the study, named Brand A and Brand B. Quality control (QC) test results for diclofenac sodium tablets show that both Brand A and Brand B conform to the United States Pharmacopeia (USP) standards. In terms of weight variation, Brand A and B have an above the mean weight limit variation of 2.79% and 2.05%, respectively. The lower mean weight limit variations are 1.21% and 1.27%, respectively, which are within the 10% standard limits of USP. Friability tests show that Brands A and B have an average friability of 0.062% and 0.01% mass loss, which are within the 1% mass loss limits of USP. In terms of drug assay, both Brands A and B fall under the USP parameter of 85%-115%, respectively. The disintegration test shows that Brand A and Brand B fall within a 15-minute time interval segment with disintegration time calculated as 6.69 min and 7.02 min for Brands A and B, respectively. Brand B of Diclofenac Sodium has a drug dissolution percentage of 90.7% within a 45-min sampling time interval. Brands A and B pass the pharmacopeia limits set under the USP standards. The friability test shows that the loss of mass for both Brands A and B was within the 1% standard limit. Similarly, with regard to weight variation, both brands conform under the normal limit of 10% above or lower the mean weight. In terms of drug assay, both brands' drug availability was within the specified 85%-115% standard range. They passed the disintegration and dissolution test within a time limit of less than 15 minutes and 45 minutes, respectively.


Achieving target levels for vascular risk parameters in Polish school-age children with type 1 diabetes - a single center study.
Background Therapeutic goals have been established to decrease the risk of long-term complications of type 1 diabetes (T1DM). The effects of these guidelines should be constantly evaluated. Hence, the present study examines the frequency at which children with T1DM treated by one of the Polish reference centers complied with the therapeutic targets issued in 2014 by the International Society for Pediatric and Adolescent Diabetes (ISPAD) and by the Diabetes Poland (PTD). Methods A retrospective analysis (years 2011-2014) was performed in patients with T1DM aged 6.5-18 years, with diabetes duration >12 months and no change of insulin regimen within 6 months. Collected data included insulin therapy regimen, weight, height, blood pressure, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and glycated hemoglobin (HbA1c) level from the last hospitalization. Results The records of 447 patients (260 boys, 299 treated with insulin pump) were analyzed. All ISPAD goals were achieved by 123 (27.5%) patients, but only 43 (9.6%) met all PTD targets. Optimal HbA1c was achieved by 224 (50.1%) according to ISPAD criteria (HbA1c<7.5%) and by 87 (19.6%) patients according to PTD (HbA1c≤6.5%). Obesity was diagnosed in 11.6% of the patients; 19.7% of the patients were overweight. In logistic regression, patient age was the only independent predictor of failing to achieve complete T1DM control (p=0.001, OR=1.12 [1.05-1.23]) and optimal HbA1c (p=0.01, OR=1.1 [1.0-1.2]) according to ISPAD guidelines. Moreover, girls had a greater risk of failing body mass index (BMI) targets (PTD: p=0.002, OR=2.16; ISPAD: p=0.0001, OR=3.37) and LDL-C targets (p=0.005, OR=1.8) than boys. Conclusions Overall, control of vascular risk factors in Polish children with T1DM is unsatisfactory. While too few children are achieving the HbA1c target set by PTD, it is possible that such strict national target helps half of the Polish school-age patients achieve ISPAD-issued aim which is more liberal. High prevalence of overweight among children with T1DM warrants initiatives focused not only on glycemic control but also on motivation of patients to lead a healthy lifestyle.


Spatial analysis, coupling coordination, and efficiency evaluation of green innovation: A case study of the Yangtze River Economic Belt.
Green innovation is an important driving force to promote the sustainable development of urban society and economy. This paper constructs an evaluation index system containing social undesirable outputs, and uses the Super-SBM model and the Malmquist-Luenberger index to evaluate green innovation efficiency in 42 cities along the Yangtze River Economic Belt from 2013 to 2017. Additionally, spatial autocorrelation analysis is used to study the spatial correlation of green innovation efficiency. Finally, the coupling coordination degree model is used to study the coupling coordination degree between green innovation efficiency and high-tech industries. The following results were obtained. (1) The average value of green innovation efficiency increased from 1.0446 to 1.0987, and the annual average growth rate of total factor productivity of green innovation was 1.1%. (2) Green innovation efficiency of the Yangtze River Economic Belt had a significant spatial positive correlation, but the types of agglomeration among cities in different sections of the Yangtze River were quite different. (3) The coupling coordination degree between green innovation efficiency and the development level of high-tech industries in the cities of the Yangtze River Economic Belt was in the basic coordination stage. Based on the research results, we suggest that cities in this belt further enhance the interactive relationship between green innovation and economic development and promote the coordinated development of economy and society.


Detection of a reactive metabolite of misonidazole in hypoxic mammalian cells.
A misonidazole metabolite capable of reacting with guanosine has been detected in extracts of Chinese hamster ovary cells exposed to misonidazole under hypoxic conditions. A misonidazole metabolite with identical chromatographic properties and reactivity with guanosine has been detected in earlier studies with misonidazole reduced to the hydroxylamine state by chemical, radiolytic, or electrolytic means. The proposed structure of the guanosine product involves the addition of a two-carbon fragment between the N1 and N2 positions of guanosine. Rearrangement of the N-hydroxy derivative of misonidazole to a C-hydroxy derivative is postulated as the initial step in the reaction scheme.


[Case of ventricular fibrillation in patients with brugada type electrocardiogram during surgery].
We described a case of ventricular fibrillation in patients with Brugada type electrocardiogram (ECG) during surgery. A 63-year-old man underwent lung lobectomy under combined general and epidural anesthesia. His preoperative ECG showed Brugada type, but he was asymptomatic and did not have a family history of sudden death. Anesthesia was induced using propofol, vecuronium and fentanyl, and maintained using propofol and lidocaine via epidural catheter. One hour into operation, ventricular fibrillation developed. After cardiac compression in a few seconds, sinus rhythm was restored and blood pressure was elevated. When the wound was sutured, ventricular fibrillation occurred again. Defibrillation was attempted immediately and sinus rhythm was restored. We diagnosed coronary spastic angina after acetylcholine challenge test. Previous report describes that the incidence of vasospasm in Brugada type ECG cases is relatively higher than those with the normal ECG. In addition, ventricular fibrillation might be induced by local anesthetics because these agents were administrated 10 minutes before the few events and balance of autonomic nervous system was changed. We conclude that strict monitoring and immediate treatment for ventricular fibrillation are important for anesthetic management in asymptomatic patient with Brugada type ECG.


Type III procollagen N-terminal peptides in experimental pulmonary fibrosis and human respiratory diseases.
In order to detect the fibrotic response in lung-tissue, concentrations of type III procollagen N-terminal peptide (P-III-P) were examined in sera and bronchoalveolar lavage fluids from rabbits with bleomycin-induced pulmonary fibrosis, and in sera from patients with various respiratory diseases, using a radioimmunoassay method. In the bleomycin-induced pulmonary fibrosis, a significant (p less than or equal to 0.05) rise in P-III-P levels was observed in the lavage fluid at 7 days, and in the sera at 21 days after bleomycin treatment, with histological confirmation of pulmonary fibrosis. Many of the patients with pulmonary fibrotic changes had significantly elevated serum P-III-P level. In lung cancer patients, most of the post-radiation serum samples were found to have P-III-P levels greater than or equal to 18 ng/ml. These results suggest that the increase in P-III-P levels is the reflection of fibrotic changes in the lungs and that the clinical assessment of serum P-III-P level could be important in the early detection of pulmonary fibrosis.


Rational Design of the Robust Janus Shell on Silicon Anodes for High-Performance Lithium-Ion Batteries.
The high-capacity silicon anode is regarded as a promising electrode material for next-generation lithium-ion batteries. Unfortunately, its practical application is still severely hindered by electrode fracture and unstable solid electrolyte interphase during cycling. Herein, we design a structure of encapsulating silicon in a robust "janus shell", in which an internal graphene shell with sufficient void space is used to absorb the mechanical stress induced by volume expansion, and the conformal carbon outer shell is introduced to strongly bond the loosely stacked graphene shell and simultaneously seal the nanopores on the surface. With the ultrastable janus carbon shell, the excellent structural integrity of the electrode and stable solid electrolyte interphase layer could be effectively preserved, resulting in an impressive cycling behavior. Indeed, the as-synthesized anodes demonstrate superior cycle stability and excellent rate performance, delivering a high reversible capacity of 1416 mA h g-1 at a current density of 0.2 A g-1 and 852 mA h g-1 at a high current density of 5 A g-1. Remarkably, the superior capacity retention of 88.5% could be achieved even after 400 cycles at a high current density of 2 A g-1. More importantly, this work opens up a novel avenue to address high-capacity anodes with a large volume change.


Green synthesis of silver nanoparticles via plant extracts: beginning a new era in cancer theranostics.
With the development of the latest technologies, scientists are looking to design novel strategies for the treatment and diagnosis of cancer. Advances in medicinal plant research and nanotechnology have attracted many researchers to the green synthesis of metallic nanoparticles due to its several advantages over conventional synthesis (simple, fast, energy efficient, one pot processes, safer, economical and biocompatibility). Medicinally active plants have proven to be the best reservoirs of diverse phytochemicals for the synthesis of biogenic silver nanoparticles (AgNPs). In this review, we discuss mechanistic advances in the synthesis and optimization of AgNPs from plant extracts. Moreover, we have thoroughly discussed the recent developments and milestones achieved in the use of biogenic AgNPs as cancer theranostic agents and their proposed mechanism of action. Anticipating all of the challenges, we hope that biogenic AgNPs may become a potential cancer theranostic agent in the near future.


Outline of medical standards for divers.
Information required for the medical examination of sport, commercial, and military divers is provided. The paper adheres to an outline format and covers the diver's medical history as well as specific points to look for in the physical and laboratory examination. Numerous disqualifying conditions are listed and they are divided into absolute contraindications and relative contraindications. Physical work capacity standards are also included as well as pressure and oxygen testing. References have been drawn from the international literature, and sources of additional medical information are provided.


Concomitant Infections With Canine Parvovirus Type 2 and Intracellular Tick-Borne Pathogens in Two Puppy Dogs.
In this report the concomitant infection with canine parvovirus type 2 (CPV-2), Hepatozoon canis and Ehrlichia canis in two puppy dogs from Southern Italy is described. Dogs were referred to a veterinary university hospital for the acute onset of lethargy and gastrointestinal signs. A complete clinical and clinicopathological evaluation was carried out and the multiple infection was confirmed by microscopic detection of inclusion bodies in peripheral blood smear, rapid immunoenzymatic tests, indirect fluorescent antibody tests, and molecular assays. Sequence analysis revealed that the CPV-2 identified belonged to the 2c variant and had amino acid residues in the predicted VP2 protein typical of "Asian-like" strains widespread in Asia and occasionally reported in Romania, Nigeria and Italy, particularly in the region of Sicily. Numerous monocytes were infected by both H. canis gamonts and E. canis morulae, suggesting that this co-infection is not accidental and that E. canis preferably infects those cells parasitized by H. canis. The clinical presentation of these animals was severe but supportive cares associated with early etiological therapy allowed a good prognosis. Movement of puppies from geographic areas where vector-borne pathogens are endemic must be carefully evaluated and core vaccinations and ectoparasite prevention treatments must be rigorously adopted.


Voltage induced anomalous conductance switching behaviour in nematic liquid crystal-multiwalled carbon nanotube composite.
Investigations on the voltage induced conductance switching behavior in the nematic liquid crystal-multiwalled carbon nanotube composite have performed. We have found that, the system formed electrical conduction pathways with increasing voltages. Anomalous conductance switching took place at a certain threshold voltage. Percolation threshold voltage depends on the frequencies of the measuring electric field. We have made an analogy between concentration dependent percolation and voltage induced percolation. A two dimensional (2D) renormalization model calculation reveals that if the CNTs form a 2D network then percolation threshold concentration (p(c)) should be 0.768. After careful analysis we have found that voltage analogy of percolation threshold concentration in our system is also very close to the above value. The connectivity exponent (beta) for 2D site percolation agrees well with our proposed voltage induced percolation connectivity exponent. Which gives a glimpse that voltage induced percolating network may forms a two dimensional network in this particular system.


Semen characteristics of gossypol-treated langurs (Presbytis entellus entellus Dufresne).
Gossypol isolated from cottonseed was fed to sexually adult male langurs at 50 and 100 mg/kg body weight per day for 90 days. Semen was collected every 2 wk, and the observations made on semen characteristics showed gossypol's detrimental effect. The gossypol administration caused a significant decline in percent sperm cells motility and a significant rise in abnormalities. The semen characteristics returned to normal levels during a 180-day recovery period following the discontinuation of gossypol treatment. A clear relationship exists between the inhibition of sperm cell motility and dose as well as duration of gossypol treatment. The testicular biopsies taken from two langurs after 90 days of gossypol treatment showed normal histoarchitecture at both the dose levels.


Hyper-beta-alaninemia associated with beta-aminoaciduria and gamma-aminobutyricaciduria, somnolence and seizures.
Hyper-beta-alaninemia was found in a somnolent, convulsing infant. Hyper-beta-aminoaciduria (beta-ala, betaAIB and taurine) was also observed, varying directly with plasma beta-alanine concentration. The beta-aminoaciduria is explained by the interaction between beta-alanine and a specific cellular-transport system with preference for beta-amino compounds. Gamma-aminobutyricaciduria was also observed, its excretion being independent of beta-alanine levels. Dietary modifications, pyridoxine, pantothenic acid and antibiotic therapy were not beneficial. Post-mortem tissues had elevated levels of beta-alanine and carnosine; GABA levels in brain were probably elevated for the age of the patient. A proposed block in beta-alanine-alpha-ketoglutarate transaminase would expand the free beta-alanine pool, thus increasing tissue carnosine. beta-Alanine is a central-nervous-system depressant. Associated inhibition of GABA transaminase and displacement of GABA from central-nervous-system binding sites would produce GABAuria and convulsions.


Estimation of atmospheric mixing heights using data from airport meteorological stations.
In this study, ground and sounding meteorological data at the Beijing Airport during 1991 to 1995 were used for estimating the local atmospheric mixing heights. Three methods were compared for this purpose, including the dry adiabatic method, the Nozaki model, and a modified Nozaki model. The modification of the Nozaki model included joint frequencies for wind-velocity and stability based on the complexities of local meteorological conditions. The estimated values from the three methods were verified through the data measured by the Beijing Meteorological Center. The results indicated that the dry adiabatic method has the best performance. The modified Nozaki model was better than the commonly used. This study is a new attempt in utilizing airport meteorological data to estimate atmospheric mixing heights.


Midlife vascular risk factors and late-life mild cognitive impairment: A population-based study.
To evaluate the impact of midlife elevated serum cholesterol levels and blood pressure on the subsequent development of mild cognitive impairment (MCI) and to investigate the prevalence of MCI in elderly Finnish population, applying the MCI criteria devised by the Mayo Clinic Alzheimer's Disease Research Center. MCI has been considered as a predictor of AD. Vascular risk factors may be important in the development of cognitive impairment and AD. However, the role of vascular risk factors in MCI and the prevalence of MCI still remain virtually unknown. Subjects were derived from random, population-based samples previously studied in surveys carried out in 1972, 1977, 1982, and 1987. After an average follow-up of 21 years, 1,449 subjects aged 65 to 79 years were reexamined in 1998. Eighty-two subjects, 6.1% of the population (average age, 72 years) met the criteria for MCI. Midlife elevated serum cholesterol level (> or =6.5 mmol/L) was a significant risk factor for MCI (OR, 1.9; 95% CI, 1.2 to 3.0, adjusted for age and body mass index); the effect of systolic blood pressure approached significance. Data point to a role for midlife vascular risk factors in the development of MCI in late life.


Degradation of polyethylene microplastics in seawater: Insights into the environmental degradation of polymers.
Microplastic contamination of aquatic environments has become an increasingly alarming problem. These, defined as particles <5 mm, are mostly formed due to the cracking and embrittlement of larger plastic particles. Recent reports show that the increasing presence of microplastics in the environment could have significant deleterious consequences over the health of marine organisms, but also across the food chain. Herein, we have studied the effects of artificial seawater on polyethylene (PE)-based beads by exposing them up to eight weeks to saltwater in stirred batch reactors in the dark and examined the structural and morphological changes these endured. Electron microscopy observations showed that artificial seawater induces severe microcracking of the pellets' surfaces. Additionally, Fourier transform infrared spectroscopy (FTIR) analyses evidenced the formation of oxidized groups whenever these particles were exposed to water and an increase in organic matter content of the waters in which the pellets were kept was evidenced by Raman spectroscopy. There were also noticeable consequences in the thermal stability of the polyethylene pellets, as determined by thermogravimetric studies (TGA). Furthermore, the parallel exposure of polyethylene pellets to UV radiation yielded less pronounced effects, thus underscoring its lower preponderance in the degradation of this material. These results highlight the importance of determining the mechanisms of degradation of microplastics in marine settings and what the implications may be for the environment. Overall, the herein presented results show that a relatively short period of time of accelerated exposure can yield quantifiable chemical and physical impacts on the structural and morphological characteristics of PE pellets.


Aldosterone and its metabolism in spontaneously hypertensive rats (SHR).
The development of hypertension in spontaneously hypertensive rats (SHR) was blocked by adrenalectomy and restored with aldosterone treatment. The blood pressures of normotensive strains of rat were not affected by aldosterone. Infusions of 10 micrograms aldosterone/day into adrenalectomized (ADX)--SHR, Wistar Kyoto (WKY) and Sprague-Dawley (SD) rats completely suppressed plasma renin activity in all strains and lowered plasma potassium levels to below normal in WKY and SD rats; aldosterone treated SHR were normokalemic. In acute studies, SHR responded normally to the antinatriuretic actions of aldosterone but gave a shallower kaliuretic response compared with WKY and SD rats. The urine of ADX-SHR injected with 3H-aldosterone contained a larger proportion of polar neutral metabolites of aldosterone than WKY urine but smaller amounts of acidic and sulfate metabolites. HPLC of the neutral metabolites showed that several polar compounds were present in larger amounts in SHR urine but that unmetabolized aldosterone was less than in WKY urine.


Nurse Practitioner Care Model: Meeting the Health Care Challenges With a Collaborative Team.
In today's environment, organizational delivery systems must produce high-quality, efficient, and cost-effective services. Central to restructuring care delivery is the evolving role of the nurse practitioner (NP) and the integration of the role as part of the health care workforce. The NP Care Model was designed and introduced to the organizational workforce in a medical center to coordinate, manage, and monitor the outcomes of high-risk patients with chronic disease efficiently. This program focused specifically on patients with heart failure who were discharged to home and identified to be at high-risk for early readmissions. The Healthy Heart Initiative prograrr coordinated by the NP addressed targeted causes of rehospitalization (lifestyle, medication and diet noncompliance, and lack of self-care disease management). The program objective of improved financial performance were met by reducing the 30-day readmission rate. Operational effectiveness and quality patient outcomes were met through the design and implementa tion of the NP Care Model, and overall patient reported satisfaction.


Analysis of the air flow generated by an air-assisted sprayer equipped with two axial fans using a 3D sonic anemometer.
The flow of air generated by a new design of air assisted sprayer equipped with two axial fans of reversed rotation was analyzed. For this goal, a 3D sonic anemometer has been used (accuracy: 1.5%; measurement range: 0 to 45 m/s). The study was divided into a static test and a dynamic test. During the static test, the air velocity in the working vicinity of the sprayer was measured considering the following machine configurations: (1) one activated fan regulated at three air flows (machine working as a traditional sprayer); (2) two activated fans regulated at three air flows for each fan. In the static test 72 measurement points were considered. The location of the measurement points was as follow: left and right sides of the sprayer; three sections of measurement (A, B and C); three measurement distances from the shaft of the machine (1.5 m, 2.5 m and 3.5 m); and four measurement heights (1 m, 2 m, 3 m and 4 m). The static test results have shown significant differences in the module and the vertical angle of the air velocity vector in function of the regulations of the sprayer. In the dynamic test, the air velocity was measured at 2.5 m from the axis of the sprayer considering four measurement heights (1 m, 2 m, 3 m and 4 m). In this test, the sprayer regulations were: one or two activated fans; one air flow for each fan; forward speed of 2.8 km/h. The use of one fan (back) or two fans (back and front) produced significant differences on the duration of the presence of wind in the measurement point and on the direction of the air velocity vector. The module of the air velocity vector was not affected by the number of activated fans.


Sampling the difficult-to-sample.
Difficult-to-sample populations are defined as rare populations or populations that are difficult to locate, enumerate or interview. This definition includes subgroups of the United States population that are at increased risk of adverse health effects associated with malnutrition. Examples include persons who are rare (pregnant women), difficult to locate (migrant farm workers), difficult to enumerate (homeless individuals) or difficult to interview (substance abusers). Probability methods to sample rare and elusive populations are reviewed briefly. Methods include disproportionately allocated sampling, multiplicity sampling and the use of multiple frames. The advantages and disadvantages of nonprobability sampling methods are compared using criteria typically applied to assess alternative probability sampling methods. The cost of data collection alone may prohibit consideration of probability sampling methods, but caution is urged before abandoning this statistically sound approach to sample selection. Considerations for sampling the difficult-to-sample are illustrated for one such population, the homeless.


Identification and quantification of phosphatidylethanolamine-derived glucosylamines and aminoketoses from human erythrocytes--influence of glycation products on lipid peroxidation.
While the Maillard reaction of amino acids and proteins as well as its consequences in vivo has been thoroughly investigated, little attention has so far been paid to the glycation of aminophospholipids such as phosphatidylethanolamine (PE) or phosphatidylserine (PS), which are essential for structure and functionality of biological membranes. PE-derived glucosylamines (Schiff-PEs) and aminoketoses (Amadori-PEs) have now for the first time been simultaneously identified and quantified in erythrocytes from diabetics and healthy individuals by liquid chromatography-electrospray mass spectrometry (LC-(ESI)MS). The amounts of glycated PE (gPE) were significantly higher in diabetics (0.18-34.2 mol% Schiff-PE and 0.047-0.375 mol% Amadori-PE) than in controls (0.12-3.99 mol% Schiff-PE and 0.018-0.055 mol% Amadori-PE). A positive correlation between fructosylated hemoglobin (HbA(1c)) and the gPE levels was established. No advanced glycation endproducts (AGEs) like 5-hydroxymethylpyrrole-2-carbaldehyde (pyrrole-PE), carboxymethyl (CM-PE), or carboxyethyl (CE-PE) derivatives were detected. To investigate the influence of gPE on lipid peroxidation of biological membranes, liposomes consisting of soy-PE and synthetically prepared Amadori-PE (16:0-16:0) were incubated for several days and the formation of oxidation products was monitored. It could be shown that Amadori-PE extensively promotes lipid peroxidation even in the absence of transition metal ions like Cu(2+) and Fe(3+). Oxidative damage to membrane lipids therefore is supposed to be at least partially caused by the glycation of aminophospholipids.


Identification of 40 genes on a 1-Mb contig around the IL-4 cytokine family gene cluster on mouse chromosome 11.
Five related cytokine genes, interleukin 3 (Il3), interleukin 4 (Il4), interleukin 5 (Il5), interleukin 13 (Il13), and granulocyte-macrophage colony-stimulating factor (Csfgm or Csf2), are tightly linked on mouse chromosome 11. We now describe a 1-Mb transcript map of this cytokine cluster. Genomic clones obtained by screening mouse bacterial artificial chromosome (BAC) and P1-derived artificial chromosome (PAC) libraries were subcloned into the pSPL3 expression vector and transfected into COS7 cells for exon trapping. In total, 118 distinct, putative exons were sequenced and characterized, mapping up to 29 distinct genes to the mouse cluster, including Il4 and Csf2. Northern blot and RT-PCR analyses indicate that all of these genes are expressed. Analysis of 1 Mb of published sequence from the region of conserved synteny on human chromosome 5q31-q33 identified 45 gene candidates, including 35 expressed genes in the human IL-4 cytokine gene cluster. Probes for 20 human genes were tested for cross-hybridization to murine BAC and PAC clones, thereby mapping 11 additional genes to the mouse complex. Thus, a total of 40 genes including 6 cytokine genes have been physically mapped within 1 Mb of mouse chromosome 11. Gene order in this complex is similar, but not identical, between human and mouse. The integrated physical and transcript maps should prove valuable as a complement to genomic sequencing and expression-dependent transcript maps of this segment of the genome.


A Citizen Science Approach to Identifying Indoor Environmental Barriers to Optimal Health for under 5s Experiencing Homelessness in Temporary Accommodation.
The first five years of life are critical for optimal growth, health, and cognitive development. Adverse childhood experiences, including experiencing homelessness, can be a risk factor for multiple health issues and developmental challenges. There is a dearth of data collected with and by families with children under age five living in temporary accommodation due to experiencing homelessness (U5TA) describing indoor environmental barriers that prevent U5TA from achieving and maintaining optimal health. The aim of this study was to address this current gap using a citizen science approach. Fifteen participants, who were mothers of U5TA living in a deprived area of London, and the lead researcher collected data in late 2019/early 2020 using: (I) a housing survey conducted via a mobile app; (II) house visits; and (III) collaborative meetings. Data were analyzed using thematic analysis. Key themes included: overcrowding/shared facilities, dampness/mold growth, poor/inadequate kitchen/toilet facilities, infestations/vermin, structural problems/disrepair, unsafe electrics, excessively cold temperatures, and unsafe surfaces that risk causing trips/falls, with all participants experiencing multiple concurrent indoor environmental barriers. The citizen science approach was successfully used to collect meaningful data demonstrating the need for child-centered housing policies meeting the needs of current and future generations of families living in TA.


Nanotubols under H2O2 exposure: is it possible to poly-hydroxylate carbon nanotubes?
We present a combined experimental and theoretical study dedicated to analyze the variations in the surface chemistry of hydroxylated multiwalled carbon nanotubes (MWCNTs), so called nanotubols, when exposed to H2O2 at high temperatures. The formation, surface density, and distribution of oxygen-containing functional groups are studied by infrared (IR) and X-ray photoelectron spectroscopy (XPS), as well as density functional theory (DFT) calculations performed on model functionalized carbon nanotubes (CNTs). After H2O2 exposure, the initial composition of -OH, -C[double bond, length as m-dash]O, and -COOH substituents notably changes, with carbonyl -C[double bond, length as m-dash]O groups being the ones that show the most notable increase on the carbon surface. Our highly oxidized MWCNTs are partially soluble and form complex two-dimensional patterns at the air-water interface, as evidenced by Brewster angle microscopy. In a second step, these films can be transferred to solid substrates to form porous multilayered carbon nanostructures with complex morphologies. In particular, and for the first time, we report the synthesis of "stadium-like" configurations made of MWCNT units whose formation and stability are a direct consequence of the self-assembly process occurring at the air/water interface. DFT calculations suggest the formation of molecular islands of oxygen-containing functional groups on the CNT surface. In addition, nudged elastic band studies reveal that, for these adsorbed phases, the reaction between two neighboring OH groups to produce atomic oxygen and a physisorbed water molecule is characterized by energy barriers of ∼0.2 eV. These small values could be at the origin of the sizable increase in chemisorbed single-oxygen species determined by XPS data after H2O2 treatment at 60 °C. The simulation of the C 1s binding energies (BE) allows us to more clearly identify the different oxygen-containing functionalities as well as to reveal how the local atomic environment affects their characteristic BEs. Even if we were unable to polyhydroxylate our carbon nanotubes, we believe that H2O2-treated MWCNTs are interesting materials for more complex post-functionalization procedures that might lead to the fabrication of novel carbon nanostructures.


Evaluation of the effect of mitomycin-C on the bioavailability of technetium-99m-labelled sodium pyrophosphate in mice.
We have reported that drugs alter the biodistribution of radiopharmaceuticals used in diagnostic imaging in nuclear medicine. Knowledge of such altered biodistribution is important in making diagnostic from scintigraphy. Mitomycin-C is used as component of many chemotherapeutic regimens to treat different tumors. The biological activities of mitomycin-C can be explained by its ability to inhibit deoxyribonucleic acid synthesis. Since patients on chemotherapeutic treatment can be submitted to nuclear medicine procedures, we studied the mitomycin-C effect on the bioavailability of the technetium-99m-labelled sodium pyrophosphate (9mTc-PYP) using an animal model. Mitomycin (0.45 mg) was administered by ocular plexus way Balb/c mice. One hour after the last dose, 99mTc-PYP (7.4 MBq) was administered and after 0.5 hr the animals (n = 15) were rapidly sacrificed. The organs were isolated, the radioactivity counted in a well counter and the percentage of radioactivity (%ATI) calculated. The results have shown that in the treated animals the %ATI has been decreased in spleen, thymus, heart and brain and increased in lung, liver and bone. The effect of this chemotherapeutic drug on the 99mTc-PYP biodistribution was statistically significant (Wilcoxon test, p < 0.05) and it could be explained by the metabolization or therapeutic action of mitomycin-C.


Endocrine testicular function in vivo and in vitro in infertile men.
In order to detect any possible Leydig cell dysfunction associated with male infertility, the endocrine capacity of the tests was investigated in vivo and in vitro in 21 infertile men. Plasma testosterone was determined before and after 3 days of hCG stimulation. Testicular tissue obtained by bilateral biopsies was subjected to (1) histological examination, (2) determination of basal testosterone concentration and (3) incubation with hCG. Patients were grouped according to histology. In vitro basal and stimulated testicular testosterone was similar in patients with normal histology, Sertoli-cell-only syndrome and spermatogenic arrest. Tissue from patients with Leydig cell hyperplasia showed 3-fold higher basal testosterone levels and a greater response to hCG. All patients had plasma testosterone levels and responses to hCG in the normal range. There was no significant correlation between the data obtained in vivo and in vitro, indicating that testosterone determinations in peripheral blood do not necessarily reflect the intratesticular situation. There was no evidence for gross abnormality in Leydig cell function accompanying disturbed spermatogenesis.


Comparison of mass spectral techniques using organic peroxides related to artemisinin.
The mass spectra of three peroxides related to artemisinin (1) are compared in nine different ionization modes. Ion trap mass spectrometry (MS/MS) spectra reveal numerous pathways for the electron impact (EI) decompositions. In the EI mode, the best spectra are obtained by using the ion trap mass spectrometer at low temperatures. Loss of oxygen is observed with the other EI spectrometers, suggesting catalytic decomposition in the ion source. Methane positive and negative chemical ionization (CI) spectra show considerable fragmentation, while isobutane CI spectra show only (M + H)+ for 1 and (M + H - H2O)+ for dihydroartemisinin (2) and (3). An unusually abundant (2M + H)+ is observed for 1 in both positive-ion plasma desorption and fast atom bombardment mass spectra.


Urinary potassium excretion and risk of developing hypertension: the prevention of renal and vascular end-stage disease study.
Previous prospective cohort studies on the association between potassium intake and risk of hypertension have almost exclusively relied on self-reported dietary data, whereas repeated 24-hour urine excretions, as estimate of dietary uptake, may provide a more objective and quantitative estimate of this association. Risk of hypertension (defined as blood pressure ≥140/90 mm Hg or initiation of blood pressure-lowering drugs) was prospectively studied in 5511 normotensive subjects aged 28 to 75 years not using blood pressure-lowering drugs at baseline of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study. Potassium excretion was measured in two 24-hour urine specimens at baseline (1997-1998) and midway during follow-up (2001-2003). Baseline median potassium excretion was 70 mmol/24 h (interquartile range, 57-85 mmol/24 h), which corresponds to a dietary potassium intake of ≈91 mmol/24 h. During a median follow-up of 7.6 years (interquartile range, 5.0-9.3 years), 1172 subjects developed hypertension. The lowest sex-specific tertile of potassium excretion (men: <68 mmol/24 h; women: <58 mmol/24 h) had an increased risk of hypertension after multivariable adjustment (hazard ratio, 1.20; 95% confidence interval, 1.05-1.37), compared with the upper 2 tertiles (Pnonlinearity=0.008). The proportion of hypertension attributable to low potassium excretion was 6.2% (95% confidence interval, 1.7%-10.9%). No association was found between the sodium to potassium excretion ratio and risk of hypertension after multivariable adjustment. Low urinary potassium excretion was associated with an increased risk of developing hypertension. Dietary strategies to increase potassium intake to the recommended level of 90 mmol/d may have the potential to reduce the incidence of hypertension.


Arizona's three-year medical curriculum: a postmortem.
The College of Medicine at the University of Arizona was among many medical schools instituting a course of study leading to graduation in three years. Students and faculty found the three-year program to be an unsatisfactory educational experience. Among the major problems were excessive intensity of classroom work, insufficient vacation time, and inadequate time to teach important basic science material. Objective measures of student performance demonstrated no differences between graduates of the new program and students graduating from a traditional four-year curriculum. A process of curriculum review involving students, faculty, and administrators ultimately resulted in several curricular improvements and establishment of a new four-year program.


Synthesis of highly efficient Ag@AgCl plasmonic photocatalysts with various structures.
By means of a simple ion-exchange process (using different precursors) and a light-induced chemical reduction reaction, highly efficient Ag@AgCl plasmonic photocatalysts with various self-assembled structures-including microrods, irregular balls, and hollow spheres-have been fabricated. All the obtained Ag@AgCl catalysts were characterized by means of X-ray diffraction, X-ray photoelectron spectroscopy, scanning electron microscopy, and UV-visible diffuse reflectance spectroscopy. The effect of the different morphologies on the properties of the photocatalysts was studied. The average content of elemental Ag in Ag@AgCl was found to be about 3.2 mol %. All the catalysts show strong absorption in the visible-light region. The obtained Ag@AgCl samples exhibit enhanced photocatalytic activity for the degradation of organic contaminants under visible-light irradiation. The stability of the plasmonic photocatalysts was also investigated in detail.


Nanofiltration of the Remaining Whey after Kefir Grains' Cultivation.
Acid whey is derived from fresh cheese. The proteins were isolated by a monolithic ion-exchange column. The remaining whey fraction was used as a starter culture substrate of kefir grains. The aim of this work was, firstly, to study the possibility of column replacement by a UF membrane. If we succeeded, the concentrate would be used as a starter culture substrate of kefir grains. The second part of the research was to purify the remaining solution. The idea was to separate this solution to the permeate and the concentrate by nanofiltration. Further application of both filtration streams was tested as aqueous solutions or dried matter. Chemical and microbiological analyses were performed of both the permeate and the concentrate. The permeate analyses showed that lactose had been fully removed. The aqueous permeate was not stable, mainly due to an increase of total bacteria from 103 to 106 CFU/mL. Therefore, the permeate was spray-dried. The dry permeate was added to the moisture solution in different concentrations. The results showed that up to 0.5% of the dry permeate could be added to the moisturizing solution, with negligible changes in properties having the ability to inhibit acne growth. Anaerobic digestion of industrial sludge was performed with the addition of an aqueous concentrate, which showed improvement in anaerobic fermentation.


[Characteristics of Nitrogen Deposition in Heilongjiang Liangshui National Nature Reserve].
To investigate the nitrogen deposition status in Heilongjiang Liangshui National Nature Reserve, a G78 nitrogen deposition collector was used to monitor dry particulate nitrogen deposition and wet nitrogen deposition during the growing season in 2015, and a bucket was used to monitor bulk nitrogen deposition during non-growing season. The results showed that:①Total nitrogen deposition (wet nitrogen deposition+dry particulate nitrogen deposition during the growing season and bulk deposition during the non-growing season) was 12.93 kg·(hm2·a)-1, inorganic nitrogen deposition was 8.27 kg·(hm2·a)-1 with NH4+/NO3- ratio of 1.3; organic nitrogen deposition was 4.66 kg·(hm2·a)-1, which was equivalent to 36.0% of the total nitrogen deposition. ②Total nitrogen deposition in the growing season (wet+dry particulate deposition) and non-growing season (bulk deposition) were 11.42 kg·hm-2 and 1.51 kg·hm-2respectively, which account for 88.3% and 11.7% of the total nitrogen deposition respectively. ③Total wet nitrogen deposition during the growing season was 9.28 kg·hm-2, contributing to 81.3% of the total nitrogen deposition in the growing season, and was positively correlated with precipitation (R2=0.87, P<0.001); total dry particulate nitrogen deposition in the growing season was 2.14 kg·hm-2, which was 18.7% of the total nitrogen deposition in growing season. Wet nitrogen deposition in this region is moderate compared with other regions in China, and is significantly affected by precipitation. There is a potential risk of environmental pollution in this region. Thus, environmental protection and water quality monitoring are required in the process of production.


Epidemiology of wheeze among preschool children: a population-based cross-sectional study from rural Sri Lanka.
To assess the prevalence of wheeze and factors associated with its severity among 3-6 years old children. DESIGN: A population-based, cross-sectional study using the WHO 30 cluster methodology with probability proportionate to size sampling. 36 preschools registered at the divisional secretariat offices of Anuradhapura district, Sri Lanka. We recruited 1060 preschool children from 36 preschools aged 3-6 years. We used the International Study of Asthma and Allergy in Childhood questionnaire to assess the prevalence, symptomatology and associated factors of wheeze. The study sample consisted of 548 (51.70%) male and 512 (48.30%) female children with a mean age of 4.41 (±0.66) years. At least one wheezing episode ever was reported in 323 (30.47%; 95% CI 27.71% to 33.34%) children and 247 (23.30%; 95% CI 20.79% to 25.97%) children had a wheezing attack in the preceding year. Severe episodes of wheezing were reported in 76 (7.17%; 95% CI 5.69% to 8.89%) participants. However, only 27 (35.53%; 95% CI 24.88% to 47.34%) children with severe wheezing had been diagnosed as asthmatics by a clinician. The identified independent risk factors for severe wheeze were allergic rhinitis (OR 6.90; 95% CI 3.84 to 12.40), domestic dog(s) (OR 2.34; 95% CI 1.01 to 5.40), frequent consumption of skipjack tuna (OR 1.94; 95% CI 1.11 to 3.39) and passive smoking (OR 1.70; 95% CI 0.93 to 3.11) while living in a house with a cement floor is a protective factor (OR 0.41; 95% CI 0.21 to 0.80). Wheezing commonly affects one-fourth of preschool children in rural Sri Lanka. Severe wheezing is often not diagnosed as asthma despite frequent symptoms, probably due to hesitancy in labelling preschool children as asthmatics. Allergic rhinitis, domestic dogs, frequent consumption of Skipjack tuna fish and exposure to passive smoking were independent risk factors for severe wheeze.


A Comparative Study Between Plate Osteosynthesis and Intramedullary Nailing for Diaphyseal Fracture of Radius and Ulna in Adults.
In this era of active living, industrial growth, increasing automobile accidents, and athletic activities, fractures of the forearm bones are becoming more frequent. The incidence of diaphyseal fractures of both bone forearms is reported to be approximately 10 per 10,000 persons per year, although rates may vary according to age and sex. If not properly treated, a fracture of the forearm bones might cause a serious loss of function. Therefore, to restore function, these fractures require adequate anatomical reduction and internal fixation. The majority of forearm fractures in adults are treated surgically, and various modes of internal fixation are available. In this study, we evaluated and compared the clinical, functional, and radiological outcomes of both bone forearm diaphyseal fractures treated with plate osteosynthesis and intramedullary nailing. This prospective and comparative study was conducted in a tertiary care medical teaching hospital in southern Rajasthan, India. Forty patients with diaphyseal fractures of the radius and ulna bones who presented to the casualty or orthopedic outpatient departments of our institute were included. Patients were divided into two groups, 20 patients in each group and treated by intramedullary nailing (group A) and plate osteosynthesis (group B), and regularly followed up and evaluated for clinical, functional, and radiological outcomes. Final results were calculated according to the modified Grace-Eversmann scoring system. In group A, out of 20 cases excellent score was seen in six cases (30%), good score in nine cases (45%), fair score in three cases (15%), and at last, two cases (10%) showed poor results. In group B, excellent score was in eight cases (40%), good score was in eight cases (40%), fair score was in three cases (15%), and at last, one case (5%) was poor in our study. Based on our findings, we conclude that for the treatment of diaphyseal fractures of the radius and ulna, both treatment modalities provide equally satisfactory results.


Few-cycle pulses tunable from 3 to 7 µm via intrapulse difference-frequency generation in oxide LGN crystals.
An ultrashort mid-infrared (IR) source beyond 5 µm is crucial for a plethora of existing and emerging applications in spectroscopy, medical diagnostics, and high-field physics. Nonlinear generation of such sources from well-developed near-IR lasers, however, remains a challenge due to the limitation of mid-IR crystals. Based on oxide La3Ga5.5Nb0.5O14 (LGN) crystals, here we report the generation of femtosecond pulses tunable from 3 to 7 µm by intrapulse difference-frequency generation of 7.5 fs, 800 nm pulses. The efficiency and bandwidth dependences on pump polarization and crystal length are studied for both Type-I and Type-II phase-matching configurations. Maximum pulse energy of ∼10nJ is generated at 5.2 µm with a conversion efficiency of ∼0.14%. Because of the few-cycle pump pulse duration, the generated mid-IR pulses are as short as about three cycles. These results, to the best of our knowledge, represent the first experimental demonstration of LGN in generating mid-IR ultrashort pulses.


Challenges in the diagnosis and management of cervical neuroendocrine carcinoma.
Neuroendocrine carcinoma represents about 1% all cervical cancers accounting for 100-200 diagnoses annually in the USA. Although it is uncommon, it is an aggressive histologic subtype of this otherwise favorable disease. To date, there are no prospective studies or randomized trials specific to this disease to guide standard of care management. Published literature consists of small case series mostly describing single-institution experiences. The Society of Gynecologic Oncology and Gynecologic Cancer InterGroup have issued consensus guidelines about the treatment of this disease based on the existing retrospective literature and expert opinion. Ongoing research is focused on further clarifying the best treatment regimen and defining molecular alterations of these tumors that can be exploited by novel treatment mechanisms. The objective of this manuscript is to describe this entity, review the literature, summarize current treatment recommendations, and propose possible research efforts for women with neuroendocrine cervical cancer.


The lectin binding pattern of normal and pathologically altered synovial tissue.
Light-microscopical lectin-binding studies were carried out in healthy and pathologically altered synovial tissue (osteoarthrosis, rheumatoid arthritis (RA)). Seven lectins were studied: Con A, DBA, PNA, RCA, SBA, UEA-I, and WGA. Con A and WGA mark all lining cells and the majority of subintimal synovial cells. RCA and SBA stain only a portion of lining cells, regardless of the basic pathology. The lectin PNA reacts only with RA and arthrotic material, and is thus suitable for the diagnosis of inflammatory changes in synovial tissue. UEA-1 is a consistent marker for capillary endothelium and large vessels.


[Cleft lobe sign. A curious clinical sign or an ischemic heart disease marker?].
The majority of studies have demonstrated a correlation between diagonal earlobe creases sign with coronary artery disease and atheroscleosis. Diagonal earlobe creases run from the lower pole of the external meatus, diagonally backwards to the edge of the lobe at approximately 45. The objective of this paper is review the evidence related to this interesting clinical sign.


Hemiepiphyseal reconstruction using tissue donated from fetal limbs in a murine model.
Epiphyseal reconstruction in the immature skeleton could have great clinical significance. Hemiepiphyseal reconstruction was performed in a murine model by transplanting fetal tissue to surgically created defects in postnatal mice. Reconstruction is facilitated by the existence of inbred strains. While the reconstruction as performed here did not completely restore the growth characteristics of the epiphysis, the model represents a potentially fruitful interface between basic and clinical biology.


The autoregulatory translational control element of poly(A)-binding protein mRNA forms a heteromeric ribonucleoprotein complex.
Repression of poly(A)-binding protein (PABP) mRNA translation involves the binding of PABP to the adenine-rich autoregulatory sequence (ARS) in the 5'-untranslated region of its own mRNA. In this report, we show that the ARS forms a complex in vitro with PABP, and two additional polypeptides of 63 and 105 kDa. The 63 and 105 kDa polypeptides were identified, as IMP1, an ortholog of chicken zip-code binding polypeptide, and UNR, a PABP binding polypeptide, respectively, by mass spectrometry of the ARS RNA affinity purified samples. Using a modified ribonucleoprotein (RNP) immunoprecipitation procedure we further show that indeed, both IMP1 and UNR bind to the ARS containing reporter RNA in vivo. Although both IMP1 and UNR could bind independently to the ARS RNA in vitro, their RNA-binding ability was stimulated by PABP. Mutational analyses of the ARS show that the presence of four of the six oligo(A) regions of the ARS was sufficient to repress translation and the length of the conserved pyrimidine spacers between the oligo(A) sequences was important for ARS function. The ability of mutant ARS RNAs to form the PABP, IMP1 and UNR containing RNP complex correlates well with the translational repressor activity of the ARS. There is also a direct relationship between the length of the poly(A) RNAs and their ability to form a trimeric complex with PABP, and to repress mRNA translation. UV crosslinking studies suggest that the ARS is less efficient than a poly(A) RNA of similar length, to bind to PABP. We show here that the ARS cannot efficiently form a trimeric complex with PABP; therefore, additional interactions with IMP1 and UNR to form a heteromeric RNP complex may be required for maximal repression of PABP mRNA translation under physiological conditions.


Use of templates to fabricate nanoscale spherical structures for defined architectural control.
Architectural design of biomaterial structures is essential to reach the full potential of the materials' chemical and biological properties. Clinically, these properties depend on the targeted applications of delivery, such as tissue regeneration, imaging, or cancer. To get an efficient material for biological applications, key properties are needed, such as degradability, low toxicity, cell specificity, relative efficiency, and capability of delivering multiple molecules. In recent years, significant progress has been made through either the design of the material itself (synthetic or natural polymers, dendrimers, crosslinking) or the fabrication technique (nozzle reactor, emulsion, and template). The combination of these materials and techniques results in a large variety of biomaterials that have varied shape and physico-chemical and biological properties. Nevertheless, these inherent properties are not sufficient and interest in discovering and developing new techniques that present these biomaterials in different light is now under focus. A useful strategy to prepare biomaterials with unique and novel architectures is through the use of templates that have defined geometrical features. This holds great promise, especially for the development of hollow structures, such as spheres. The nanoscale structural design of biomaterials via the use of templates and their potential clinical applications are discussed. In addition, the conceptual hurdles that must be overcome to produce applications that are clinically relevant are examined.


More practice does not necessarily enhance transfer of learning: evidence and interpretations.
The purpose of this study was to investigate what was learned and transferred of a criterion task using a transfer task and a self-paced procedure. Based on the results of two previous studies, five durations of practice were specifically selected to examine what can be transferred to a new task after different amounts of practice (40, 75, 100, 125, and 150 acquisition trials) on a criterion task. The criterion task required subjects to practice finding an 8-in. line with no fixed starting and ending points from left to right. The transfer task was different from the criterion task in two dimensions, distance (10-in. line) and direction (right to left). 50 volunteers were randomly assigned into 5 groups. Appropriate 5 x 2 (groups by blocks of practice) analyses of variance and a priori contrasts were conducted for all dependent variables (absolute error, variable error, movement time, KR-delay, post-KR interval, intertrial interval, interstimulus interval, and KR-delay by post-KR interval ratio) to examine the effects of terminal acquisition of the criterion task on the initial performance of the transfer task. Analysis indicated that, during practice, participants developed a functional interaction between performance characteristics and chronological profile of KR-delivery of the criterion task that was transferable to the transfer task. Also, practice beyond a certain point was detrimental to the ability to transfer what was learned.


Antecedent Predictors of Feeding Outcomes in Premature Infants With Protracted Mechanical Ventilation.
The aim of the present study was to define risk factors associated with gastrostomy in premature infants receiving protracted mechanical ventilation (≥30 days). Retrospective data collected on 170 preterm neonates (birth weight <1500 g) who received uninterrupted mechanical ventilation for ≥30 days were analyzed with logistic regression methods to predict the association of gastrostomy with cardiorespiratory, infectious, and neurological morbidities. A total of 32 of 170 infants had gastrostomy tubes. Including all of the covariates in 1 model, duration of cumulative ventilation (P < 0.001) and uninterrupted ventilation (P < 0.001), and ventriculoperitoneal shunt (P = 0.02) were significant predictors, whereas sepsis, intraventrical hemorrhage grade III or IV, and patent ductus arteriosus ligation were not. Respiratory severity score (mean airway pressure × fraction of inspired oxygen) calculated at 30 days of life was also a significant predictor (P = 0.01). In infants with protracted mechanical ventilation, the degree of respiratory support at 1 month of age, prolonged respiratory morbidity, and neuropathology are the significant predictors for gastrostomy.


Persistent dynamics in coupled non-degenerate parametric oscillators: pump saturation prevents mode competition.
The coherent dynamics in networks of coupled oscillators is of great interest in wave-physics since the coupling produces various dynamical effects, such as coherent energy exchange (beats) between the oscillators. However, it is common wisdom that these coherent dynamics are transients that quickly decay in active oscillators (e.g. lasers) since pump saturation causes mode competition that results, for homogeneous gain, in the prevalence of the single winning mode. We observe that pump saturation in coupled parametric oscillators counter-intuitively encourages the multi-mode dynamics of beating and indefinitely preserves it, despite the existence of mode competition. We explore in detail the coherent dynamics of a pair of coupled parametric oscillators with a shared pump and arbitrary coupling in a radio frequency (RF) experiment, as well as in simulation. Specifically, we realize two parametric oscillators as different frequency-modes of a single RF cavity and couple them arbitrarily using a digital high-bandwidth FPGA. We observe persistent coherent beats that are maintained at any pump level, even high above the threshold. The simulation highlights how the interplay of pump depletion between the two oscillators prevents them from synchronizing, even when the oscillation is deeply saturated.


Regulation of human T helper cell differentiation by antigen-presenting cells: the bee venom phospholipase A2 model.
Whereas some individuals develop immunity to bee sting and mount protective IgG4- mediated antibody responses to bee venom phospholipase A2 (PLA), others produce large amounts of PLA-specific IgE antibodies and become allergic to this, otherwise, innocuous antigen. PLA-specific IgE responses are the result of imbalanced T helper (Th)2-cell differentiation. There are multiple mechanisms driving the differentiation of naive CD4+ T cells into Th1- or Th2-cell phenotypes. Most of them are linked to the conditions occurring during initial or repeated encounters with the allergen, in the context of an antigen-presenting cell (APC). The different types of APC and their availability to display particular cytokine production profiles, pattern recognition receptors, costimulatory molecules and specific HLA haplotypes are key determinants for human Th1- and Th2-cell polarization.


Characterization and stability of solid dispersions based on PEG/polymer blends.
Solid dispersions were prepared by a melting method from the water-insoluble model drugs carbamazepine and nifedipine and polyethylene glycol 1500 (PEG 1500) or 1:1 mixtures of PEG 1500 and the polymers polyvinylpyrrolidone (PVP 30, PVP 12), polyvinylpyrrolidone-co-vinylacetate (PVPVA) and Eudragit EPO (Eudragit) in order to combine advantages of the different carrier polymers (recrystallization inhibition, processability and stability). The solid dispersions were characterized by dissolution, powder X-ray diffractometry and microscopy directly after preparation and after storage for 3 and 6 months at 25 degrees C/0% relative humidity (RH) or 3 months at 40 degrees C/75% RH. More than 80% drugs were released from all solid dispersions within 20min. The dissolution rate of carbamazepine decreased in the order of PEG 1500>PEG 1500/Eudragit>PEG 1500/PVP 30>PEG 1500/PVPVA>PEG 1500/PVP 12. The dissolution rank order was not directly correlated to the amorphous/crystalline state of the drugs, but rather to the properties of the PEG 1500/polymer compositions. Nifedipine was released in the order of PEG 1500>PEG 1500/PVPVA>PEG 1500/PVP 30>PEG 1500/PVP 12>PEG 1500/Eudragit. Amorphous nifedipine was present in all PEG 1500/polymer dispersions except in pure PEG 1500 solid dispersion. The significant increase in dissolution rate of PEG 1500 solid dispersions was due to the reduced crystallinity of the drug and the excellent solubilisation properties of PEG 1500. After 6 months storage at 25 degrees C/0% RH, the solid dispersions released both drugs in the order PEG 1500/PVPVA>PEG 1500/PVP 30>PEG 1500/PVP 12>PEG 1500/Eudragit>PEG 1500. The stabilized amorphous state of the drug resulted in stable dissolution profiles of PEG 1500/PVPVA, PEG 1500/PVP 30 and PEG 1500/PVP 12 when compared to the PEG 1500 solid dispersions, which contained a higher amount of crystalline drug. The solid dispersions with PEG 1500/PVPVA or PEG 1500/PVP stored for 3 months at 40 degrees C/75% RH showed phase separation due to the hygroscopic properties of the polymers. The influence of 10% (w/w) of the solubilisers polyoxyl 40 hydrogenated castor oil (Cremophor), macrogol-15-hydroxystearate (Solutol) and fatty alcohol alkoxylate (Pluronic) on the dissolution rate and the physical state of the drug was significant.