Evidence for an inactive transposable mariner-like element in Anopheles albimanus.
Transposable elements may eventually be used as transformation vectors of anti-Plasmodium genes in natural populations of Anopheles mosquitoes. The mariner transposable element is widespread in most animal phyla and we wished to test for its presence in the important Latin American malaria vector, Anopheles albimanus. Degenerate primers were designed from the consensus of insect mariner elements and used in a polymerase chain reaction to amplify a fragment of the predicted size from An. albimanus. The fragment was cloned, sequenced, and determined to be a mariner-like element through multiple alignment with known insect mariner elements. Dot blot and Southern blot analyses showed only one or a few elements per haploid genome. The cloned fragment was used as a probe to isolate similar sequences from an An. albimanus genomic DNA library. A 659-base-pair clone was 57% similar at the DNA level with mariner elements from Anopheles gambiae, Chrysoperla ptorapunda, and Haematobia irritans. This low sequence similarity is comparable to that found among mariner-like elements in all insects. However, conserved amino acid motifs were not discovered nor was a single open reading frame found. These aspects suggest that the An. albimanus mariner-like element may represent an ancient transposition event but that the element is no longer active, the typical open reading frame having been disrupted through nucleotide insertions and deletions.


Characterization of a flat-panel detector for ion beam spot measurements.
Dynamic beam delivery techniques are being increasingly used for cancer therapy. Scanning ion beams require extensive and time-demanding quality assurance procedures and beam tuning. Accordingly, fast measurement techniques improving the efficiency of the procedures and accommodating the safety requirements are highly desirable. Major requirements for a detector used for beam-shape measurements are high spatial resolution in two dimensions, reusability, online readout and easy handling. At the Heidelberg Ion Beam Therapy Facility (Germany), we examined the performance of the RID 256 L flat-panel detector for beam spot measurements. The two-dimensional beam profiles of proton and carbon ion beams measured were compared to measurements with radiographic films at intermediate energies using the index. The difference to the beam width measured with radiographic films of less than 3% demonstrates sufficient accuracy of ion beam width measurements possible with this detector for both proton and carbon ion beams. The beam shapes were also measured at different beam intensities. At both the highest and lowest energies available at the HIT, no beam spot-shape deformation was found with increasing beam intensities, as long as the boundary of the dynamic range was not exceeded. The signal leak along the readout direction was identified as an undesirable effect. However, due to small amplitudes and static beams, this effect is of minor importance for beam spot measurements. Distortion of results due to detector radiation damage was monitored. No detector radiation damage was observed over the experiments. Moreover, the observed short-time detector response stability (within ±0.1%) as well as medium term stability (within 0.5% in 15 months) was excellent. This flat-panel detector is compact and easy to use. Together with its low weight, this helps to speed up measurement procedures substantially. All these properties make this an ideal detector for the fast, high-resolution imaging of static ion beam spots needed for constancy measurements in daily beam quality assurance and for accelerator tuning. For daily use, radiation damage has to be monitored continuously and corrected for if necessary.


Scintigraphic evaluation of experimental colitis in rabbits.
Scintigraphic techniques are frequently used for evaluation of inflammatory bowel disease. The radiopharmaceutical of choice is labeled leukocytes. In this study, two new agents, 111In-labeled polyethylene glycol-coated liposomes and 111In-labeled human nonspecific gamma globulin (immunoglobulin G; IgG), were compared with 111In-leukocytes in a rabbit model of colitis. In rabbits, acute colitis was induced by colonic instillation of trinitrobenzene sulfonic acid at 25 cm from the anal sphincter. After 24 hr, 15 MBq of the radiopharmaceuticals was injected intravenously in groups of four rabbits. Twenty-four hours after injection, the animals were killed and macroscopic abnormalities were scored in seven consecutive affected colonic segments of 5 cm each (0 = normal, 1 = inflammation, 2 = ulcers). The ex vivo uptake was measured in the normal ascending colon and the affected colonic segments. The colitis index (CI, affected-to-normal colon-uptake ratio) was calculated. Histologically, an acute, patchy, transmural colitis was observed at the site of instillation and the distal colon. The CI of all agents in colitis lesions correlated with the severity of the abnormalities. With increasing severity, the CI for liposomes was 1.86 +/- 0.24, 4.88 +/- 0.42 and 7.42 +/- 0.54 (r2 = 0.68, p < 0.001); for leukocytes 1.77 +/- 0.32, 3.10 +/- 0.58 and 5.54 +/- 0.83 (r2 = 0.31, p < 0.01); for IgG 1.60 +/- 0.29, 2.81 +/- 0.21 and 2.65 +/- 0.21 (r2 = 0.29, p < 0.02). Indium-111-labeled-leukocytes, -IgG and -liposomes all show increased uptake in inflamed colonic tissue. Indium-111-liposomes showed the highest CI, which correlates best with the morphological abnormalities. Indium-111-leukocytes and 111In-liposomes are superior to 111In-IgG for this indication.


Treatment of patients with severe acute necrotizing pancreatitis based on prospective evaluation.
To examine the impact of a prospectively applied diagnostic and treatment protocol in patients with severe acute necrotizing pancreatitis. During a 4-year period (1993-1996), 26 patients were treated for necrotizing pancreatitis, as documented by contrast-enhanced computed tomography (CE-CT). All patients were prospectively treated by medical means. Patients with persistent systemic inflammatory response syndrome underwent fine-needle aspiration for bacterial cultures. In case of positive results operative intervention was followed, while in negative results the conservative management was continued. Fine-needle aspiration was repeated every 5-7 days if systemic inflammatory response syndrome persisted or worsened. Sixty-five patients hospitalized during the preceding 11 years (1982-1992), when such a treatment was not constantly applied, served as controls. Infected pancreatic necrosis was demonstrated in 7 of the 26 patients (27%) and was treated by open drainage and/or post-operative lavage with a mortality rate of 14.2%. Thirteen patients in whom fine-needle aspiration was not necessary and 6 with negative cultures after fine-needle aspiration (73%) followed conservative treatment and the mortality rate was 5.2%. The total mortality rate of 7.7% was significantly lower than the mortality rate of 26.2% observed in the control group (p = 0.05). Recent evolution made in the management of severe necrotizing acute pancreatitis can lead to better results in the context of a strictly applied treatment protocol. Such protocols may improve mortality and serve as controls in future study.


Expression of the proto-oncogene Pokemon in colorectal cancer--inhibitory effects of an siRNA.
This study aimed to investigate expression of the proto-oncogene POK erythroid myeloid ontogenic factor (Pokemon) in colorectal cancer (CRC), and assess inhibitory effects of a small interference RNA (siRNA) expression vector in SW480 and SW620 cells. Semi-quantitative reverse transcription-polymerase chain reaction (PCR) and immunohistochemistry were performed to determine mRNA and protein expression levels of Pokemon in CRC tissues. Indirect immunofluorescence staining was applied to investigate the location of Pokemon in SW480 and SW620 cells. The siRNA expression vectors that were constructed to express a short hairpin RNA against Pokemon were transfected to the SW480 and SW620 cells with a liposome. Expression levels of Pokemon mRNA and protein were examined by real-time quantitative-fluorescent PCR and western blot analysis. The effects of Pokemon silencing on proliferation of SW480 and SW620 cells were evaluated with reference to growth curves with MTT assays. The mRNA expression level of Pokemon in tumor tissues (0.845 ± 0.344) was significantly higher than that in adjacent tumor specimens (0.321 ± 0.197). The positive expression ratio of Pokemon protein in CRC (87.0%) was significantly higher than that in the adjacent tissues (19.6%). Strong fluorescence staining of Pokemon protein was observed in the cytoplasm of the SW480 and SW620 cells. The inhibition ratios of Pokemon mRNA and protein in the SW480 cells were 83.1% and 73.5% at 48 and 72 h, respectively, compared with those of the negative control cells with the siRNA. In the SW620 cells, the inhibition ratios of Pokemon mRNA and protein were 76.3% and 68.7% at 48 and 72 h, respectively. MTT showed that Pokemon gene silencing inhibited the proliferation of SW480 and SW620 cells. Overexpression of Pokemon in CRC may have a function in carcinogenesis and progression. siRNA expression vectors could effectively inhibit mRNA and protein expression of Pokemon in SW480 and SW620 cells, thereby reducing malignant cell proliferation.


Efficacy of fenbendazole and levamisole treatments in captive Houston toads (Bufo [Anaxyrus] houstonensis).
Effective disease monitoring and prevention is critical to the success of captive amphibian care. Nematodes, including the genera Rhabdias and Strongyloides, are known to contribute to mortality in captive amphibians and have been identified in the Houston Zoo's endangered Houston toad (Bufo [Anaxyrus] houstonensis) captive assurance colony. Five years of fecal data for the toad colony were compiled and analyzed in order to investigate the efficacy of two anthelminthic medications, fenbendazole (FBZ) and levamisole (LMS), which were used to control nematode infections. Both FBZ (dusted onto food items) and topical LMS (6.5 to 13.5 mg/kg) significantly reduced the number of nematode eggs, larvae, and adults observed by fecal parasitologic examination. There were no significant differences between treatments, and egg reappearance periods were difficult to compare as a result of low sample size. No adverse effects from either anthelminthic treatment were observed. Both topical LMS and oral FBZ appear to be safe and efficacious treatments for the reduction of the internal nematode burden in captive Houston toads.


High fluorescence cell count in pleural fluids for malignant effusion screening.
Malignant pleural effusion (MPE) is mainly secondary to pleural metastasis. Its prevalence is 15 to 35% of all the pleural effusions, and the median of survival oscillates between 4 and 6 months, reason why it is very important to know how to diagnose it. The Sysmex XN-350® is an automated hematological analyzer that allows white blood cell count and differentiation, as well as high fluorescence cells (HFC) which includes macrophages, mesothelial and neoplastic cells. For MPE screening, the best combinations obtained were HF-BF# ≥ 17/μL and HF-BF# > 10/μL, both in the absence of heart failure and/or low respiratory infection. The results of this study show that the automated analysis of the pleural fluid with the Sysmex XN-350® analyzer is effective for the screening of the MPE.


Utilizing high-fidelity crucial conversation simulation in genetic counseling training.
Genetics professionals are often required to deliver difficult news to patients and families. This is a challenging task, but one that many genetics trainees have limited opportunity to master during training. This is true for several reasons, including relative scarcity of these events and an understandable hesitation of supervisors allowing a trainee to provide such high stakes information. Medical simulation is effective in other health care disciplines giving trainees opportunities of "hands on" education in similar high stakes situations. We hypothesized that crucial conversations simulation would be effective for genetics trainees to gain experience in communication and counseling skills in a realistic clinical scenario. To test this hypothesis, we designed a prenatal counseling scenario requiring disclosure of an abnormal amniocentesis result and discussion of pregnancy management options; we challenged participants to address common counseling questions. Three medical genetics resident physicians and five genetic counseling students participated. Genetics and simulation experts observed the session via live video feed from a different room. A behavioral checklist was completed in real time assessing trainee's performance and documenting medical information discussed. Debriefing immediately followed the session and included simulation and genetics experts and the actor parents. Participants completed open-ended post evaluations. There was a trend towards participants being more likely to discuss issues the child could have while an infant/toddler rather than issues that could emerge as the child with Down Syndrome transitions to adulthood and end of life (P=.069). All participants found the simulation helpful, notably that it was more realistic than role-playing with colleagues.


D-ribose attenuates ischemia/reperfusion-induced renal injury by reducing neutrophil activation in rats.
The ischemia/reperfusion (I/R) represents a common pathological mechanism that causes renal injuries. A monosaccharide D-allose has been shown to inhibit neutrophil activation, which is involved in the I/R-induced organ injuries. We therefore examined the role of D-ribose in the I/R-induced renal injury using a rat model. D-ribose, a monosaccharide found in all living cells, serves as a key component of adenosine-5'-triphosphate and nicotinamide adenine dinucleotide. Male Wistar rats were divided into the sham, control and D-ribose groups. In the control and D-ribose groups, rats were subjected to 45 min of left renal ischemia, followed by 24 h of reperfusion, while the I/R procedure was not performed in the sham group. Rats were intravenously administered D-ribose (sham group and D-ribose group, 400 mg/kg) or saline (control group) 30 min before ischemia. Blood urea nitrogen (BUN), serum creatinine and urinary N-acetyl beta-D-glucosaminidase (NAG) were measured as indicators of glomerular function and proximal tubular function. We also measured cytokine-induced neutrophil chemoattractant-1 (CINC-1) and myeloperoxidase concentrations to assess neutrophil activation and infiltration, respectively. The tissue sections were scored to evaluate the tubular injury. In the control group, BUN, creatinine, NAG, CINC-1, myeloperoxidase, histological severity score, and number of infiltrating neutrophils were increased following I/R insult, as compared with the sham group. Such increases in biochemical markers, severity score, and infiltrating neutrophils were significantly inhibited in the D-ribose group. Thus, D-ribose ameliorates the I/R-induced renal injury probably by inhibiting neutrophil activation, and may be useful in attenuating the renal injury associated with renal ischemia.


Mutation profile of over 4500 SARS-CoV-2 isolations reveals prevalent cytosine-to-uridine deamination on viral RNAs.
Aim: The inference of coronavirus evolution is largely based on mutations in SARS-CoV-2 genome. Misinterpretation of these mutations would mislead people about the evolution of SARS-CoV-2. Materials & methods: With 4521 lines of SARS-CoV-2, we obtained 3169 unique point mutation sites. We counted the numbers and calculated the minor allele frequency (MAF) of each mutation type. Results: Nearly half of the point mutations are C-T mismatches and 20% are A-G mismatches. The MAF of C-T and A-G mismatches is significantly higher than MAF of other mutation types. Conclusion: The excessive C-T mismatches do not resemble the random mutation profile. They are likely to be caused by the cytosine-to-uridine deamination system in hosts.


Improved Characterization of Diffusion in Normal and Cancerous Prostate Tissue Through Optimization of Multicompartmental Signal Models.
Multicompartmental modeling outperforms conventional diffusion-weighted imaging (DWI) in the assessment of prostate cancer. Optimized multicompartmental models could further improve the detection and characterization of prostate cancer. To optimize multicompartmental signal models and apply them to study diffusion in normal and cancerous prostate tissue in vivo. Retrospective. Forty-six patients who underwent MRI examination for suspected prostate cancer; 23 had prostate cancer and 23 had no detectable cancer. 3T multishell diffusion-weighted sequence. Multicompartmental models with 2-5 tissue compartments were fit to DWI data from the prostate to determine optimal compartmental apparent diffusion coefficients (ADCs). These ADCs were used to compute signal contributions from the different compartments. The Bayesian Information Criterion (BIC) and model-fitting residuals were calculated to quantify model complexity and goodness-of-fit. Tumor contrast-to-noise ratio (CNR) and tumor-to-background signal intensity ratio (SIR) were computed for conventional DWI and multicompartmental signal-contribution maps. Analysis of variance (ANOVA) and two-sample t-tests (α = 0.05) were used to compare fitting residuals between prostate regions and between multicompartmental models. T-tests (α = 0.05) were also used to assess differences in compartmental signal-fraction between tissue types and CNR/SIR between conventional DWI and multicompartmental models. The lowest BIC was observed from the 4-compartment model, with optimal ADCs of 5.2e-4, 1.9e-3, 3.0e-3, and >3.0e-2 mm2 /sec. Fitting residuals from multicompartmental models were significantly lower than from conventional ADC mapping (P < 0.05). Residuals were lowest in the peripheral zone and highest in tumors. Tumor tissue showed the largest reduction in fitting residual by increasing model order. Tumors had a greater proportion of signal from compartment 1 than normal tissue (P < 0.05). Tumor CNR and SIR were greater on compartment-1 signal maps than conventional DWI (P < 0.05) and increased with model order. The 4-compartment signal model best described diffusion in the prostate. Compartmental signal contributions revealed by this model may improve assessment of prostate cancer. Level of Evidence 3 Technical Efficacy Stage 3 J. MAGN. RESON. IMAGING 2021;53:628-639.


[Absorption line intensities of phosphine in the regions 1 950-2 480 cm(-1) and 3 280-3 580 cm(-1) studied by Fourier-transform spectroscopy].
The data of line intensities of the fundamental and low overtone absorption bands of phosphine are the basic reference data for the applications in quantative analysis and astronomy. The method of high-resolution Fourier-transform spectroscopy study on the absorption line intensities is discussed. With a series of measurement and fitting the line profiles, altogether 1760 absorption lines intensities of phosphine were obtained, corresponding to five bands in the 1950-2480 cm(-1) region and four bands in the 3 280-3 580 cm(-1) region. The accuracy of the line intensities was estimated to be +/-6%.


The effects of sound therapy in tinnitus are characterized by altered limbic and auditory networks.
To determine the neural mechanism underlying the effects of sound therapy on tinnitus, we hypothesize that sound therapy may be effective by modulating both local neural activity and functional connectivity that is associated with auditory perception, auditory information storage or emotional processing. In this prospective observational study, 30 tinnitus patients underwent resting-state functional magnetic resonance imaging scans at baseline and after 12 weeks of sound therapy. Thirty-two age- and gender-matched healthy controls also underwent two scans over a 12-week interval; 30 of these healthy controls were enrolled for data analysis. The amplitude of low-frequency fluctuation was analysed, and seed-based functional connectivity measures were shown to significantly alter spontaneous local brain activity and its connections to other brain regions. Interaction effects between the two groups and the two scans in local neural activity as assessed by the amplitude of low-frequency fluctuation were observed in the left parahippocampal gyrus and the right Heschl's gyrus. Importantly, local functional activity in the left parahippocampal gyrus in the patient group was significantly higher than that in the healthy controls at baseline and was reduced to relatively normal levels after treatment. Conversely, activity in the right Heschl's gyrus was significantly increased and extended beyond a relatively normal range after sound therapy. These changes were found to be positively correlated with tinnitus relief. The functional connectivity between the left parahippocampal gyrus and the cingulate cortex was higher in tinnitus patients after treatment. The alterations of local activity and functional connectivity in the left parahippocampal gyrus and right Heschl's gyrus were associated with tinnitus relief. Resting-state functional magnetic resonance imaging can provide functional information to explain and 'visualize' the mechanism underlying the effect of sound therapy on the brain.


Solitary fibrous tumors of the pleura: clinical characteristics, surgical treatment and outcome.
The aim of this paper is to study clinical characteristics, surgical treatment and outcome of patients with solitary fibrous tumor of the pleura operated in our institutions in a 20-year period. Clinical records of all patients operated for solitary fibrous tumors of the pleura between 1981 and 2000 were reviewed retrospectively. Tumors were classified as malignant in the presence of at least one of the following criteria: (1) high mitotic activity; (2) high cellularity with crowding and overlapping of nuclei; (3) presence of necrosis; (4) pleomorphism; otherwise they were considered as benign. Sixty patients (mean age 55 years) were operated in this period. None had asbestos exposure. Symptoms were present in 31 cases. Surgical approaches included thoracotomy (n=53), video-assisted thoracoscopy (n=6), and median sternotomy (n=1). Tumors originated from visceral pleura in 48 cases, from parietal, mediastinal or diaphragmatic pleura in seven, two and three cases, respectively; their mean diameter was 8.5 cm. Tumors could be resected with their implantation basis in 49 patients. In the remaining 11, extended resections were performed, including lung parenchyma (lobectomy, n=4, pneumonectomy, n=2), osteomuscular chest wall structures (n=2), diaphragm (n=2), and pericardium (n=1). Two postoperative deaths (due to myocardial infarction and pulmonary embolism, respectively) occurred. Tumors were pathologically benign in 38 cases and malignant in 22 cases. Mean follow-up was 88 months. Resection was complete in all the patients with benign tumors and no recurrence occurred. Resection was considered as complete in 21/22 malignant tumors. Local recurrence was observed in two cases. Both could be successfully managed by iterative exeresis (no extended resection had been initially performed). Metastatic disease (responsible for patient's death) was observed following the only incomplete resection. Actuarial 5- and 10-year survival rates were 97% for benign tumors and 89% for malignant ones. Surgical resection provided cure in all the patients with benign tumors. As insufficiency of exeresis is associated with all recurrences in malignant tumors, completeness of resection is in our experience the best prognostic factor in these forms.


Self-avoiding flexible polymers under spherical confinement.
We compute the free energy of confinement for a flexible self-avoiding polymer inside a spherical cavity. Accurate numerical results allow us to arbitrate between three competing scaling predictions. For moderate confinement, the free energy exhibits a power-law dependence on cavity size that is different from what is observed for planar and cylindrical confinement. At high monomer concentrations, crossover to a different scaling regime is observed, consistent with the screening of the excluded-volume interactions. We demonstrate how our findings lead to a revised prediction for the escape time of a polymer from a spherical confinement.


Stable Indium-Pyridylcarboxylate Framework: Selective Gas Capture and Sensing of Fe3+ Ion in Water.
By employing a pyridyl-decorated dicarboxylic acid ligand, 3-(2',5'-dicarboxylphenyl)pyridine acid (H2dcpy), a three-dimensional In3+-based metal-organic framework, H3O[In3(dcpy)4(OH)2]·3DMF·4H2O (1), with a good chemical stability toward acid and base has been synthesized. The compound 1 shows an uncommon (3,8)-connected tfz-d; UO3 topological net based on linear In3(COO)4(OH)2 clusters and also contains one-dimensional open channels. Particularly, 1 contains two types of dcpy2- linkers, in which the pyridyl group in one participates in coordination with the In3+ ion, whereas that in the other is uncoordinated but hangs in the inner sides of the channels as functionalized sites. Gas adsorption experiments demonstrate that 1 is able to selectively adsorb C2H2, C2H4, and CO2 over CH4. Simultaneously, 1 shows a highly selective and sensitive fluorescence detection toward Fe3+ ion in water with good recyclability.


License to kill: Formulation requirements for optimal priming of CD8(+) CTL responses with particulate vaccine delivery systems.
Induction of CD8(+) T-cell responses is critical for the immunological control of a variety of diseases upon vaccination. Modern subunit vaccines are based on highly purified recombinant proteins. The high purity represents a major advancement in terms of vaccine safety compared to previous vaccination strategies with live attenuated or whole killed pathogens, but typically renders vaccine antigens poorly immunogenic and insufficient in mobilizing protective immunity. Adjuvants are therefore needed in vaccine formulations to enhance, direct and maintain the immune response to vaccine antigens. However, a weakness of many adjuvants is the lack of induction of CD8(+) T-cell responses against protein antigens, which are required for protection against challenging and difficult infectious diseases such as AIDS and for therapeutic cancer vaccination. Within the last decade, adjuvant systems that can induce CD8(+) T-cell responses have been developed and the first clinical trials demonstrating the clinical relevance of such formulations have been performed. This paper reviews the current status of lipid- and polymer-based particulate antigen delivery systems capable of stimulating CD8(+) T-cell immunity with special focus on mechanisms of priming and pharmaceutical requirements for optimal activation of cytotoxic T-lymphocytes that can kill virus-infected or abnormal (cancer) cells.


COVID19 Infection in Health Care Professionals: Risks, Work-Safety and Psychological Issues.
COVID-19 infection has spread widely over past 5 months to become a pandemic of global proportions affecting almost every country. While HCPs are expected to tackle this crisis by working in hospital and intensive care setting, there is real risk of them contracting infection and even dying. This article aims to report cases of healthcare personnel (HCPs) contracting COVID19 in various settings in a tertiary care hospital, a designated COVID centre, with view to disseminate information and review safety and psychological health issues of healthcare professionals. This study is a cross-sectional hospital-based survey from April 2020-June 2020. Data on demographics, workplace safety and psychological parameters from HCPs was collected by both interview and an online questionnaire form. A total of 40 healthcare workers were infected in the hospital in a period of 2 months since the first COVID case was admitted in the hospital. Almost 57.5% reported positive on several psychological parameters like anxiety, fear, anger, irritability and insomnia. About 42.5% had no psychological counselling after testing positive. These cases illustrate work-place risks for healthcare workers of acquiring COVID19 and highlight the problems faced in terms of risks of transmission to patients and colleagues, isolation of contacts in departments leading to near-breakdown of services and psychological stress to healthcare workers. Healthcare workers being at frontline of exposure to corona patients are at increased risk of developing COVID19 infections. Healthcare workers are working under tremendous stress in this pandemic and it is necessary to combat fear with facts and work towards safe work atmosphere so that they can discharge their duties to best of their ability.


Contribution of the GAVI Alliance to improving health and reducing poverty.
The Global Alliance for Vaccines and Immunization (GAVI), now 10 years old, was established as a successful and innovative public-private partnership to deal with a fundamental inequity. The poorest children in the poorest parts of the world were being denied access to life-saving vaccines simply on the basis of cost. GAVI has been successful in mobilizing significant funding from donors and through innovative financing instruments, immunizing large numbers of children. GAVI has been less successful, at least in the time frames first envisaged, at quickly reducing the prices of new and under-used vaccines to levels affordable by the poorest countries. Vaccines remain some of the most cost effective of public health interventions. As GAVI seeks to introduce a new set of vaccines to tackle major killers such as pneumonia and diarrhoea, and emerging threats such as cervical cancer, it needs to raise significant additional funds. There is no single solution. Multiple and new instruments will be required to raise finance both globally and at the country level, and also to incentivize industry and others to provide vaccines at affordable prices to the poorest countries.


Phytochemicals from Selective Plants Have Promising Potential against SARS-CoV-2: Investigation and Corroboration through Molecular Docking, MD Simulations, and Quantum Computations.
Coronaviruses have been reported previously due to their association with the severe acute respiratory syndrome (SARS). After SARS, these viruses were known to be causing Middle East respiratory syndrome (MERS) and caused 35% evanescence amid victims pursuing remedial care. Nowadays, beta coronaviruses, members of Coronaviridae, family order Nidovirales, have become subjects of great importance due to their latest pandemic originating from Wuhan, China. The virus named as human-SARS-like coronavirus-2 contains four structural as well as sixteen nonstructural proteins encoded by single-stranded ribonucleic acid of positive polarity. As there is no vaccine available to treat the infection caused by these viruses, there is a dire need for taking necessary steps against this virus. Herein, we have targeted two nonstructural proteins of SARS-CoV-2, namely, methyltransferase (nsp16) and helicase (nsp13), respectively, due to their substantial activity in viral pathogenesis. A total of 2035 compounds were analyzed for their pharmacokinetics and pharmacological properties. The screened 108 compounds were docked against both targeted proteins and were compared with previously reported known compounds. Compounds with high binding affinity were analyzed for their reactivity through DFT analysis, and binding was analyzed using molecular dynamics simulations. Through the analyses performed in this study, it is concluded that EryvarinM, Silydianin, Osajin, and Raddeanine can be considered potential inhibitors for MTase, while TomentodiplaconeB, Osajin, Sesquiterpene Glycoside, Rhamnetin, and Silydianin for helicase after these compounds are validated thoroughly using in vitro and in vivo protocols.


Magnetically Driven Tunable 3D Structured Fe3 O4 Vertical Array for High-Performance Solar Steam Generation.
Structural design of the solar-absorbing layer has been considered as one of the most direct and effective approaches for improving the solar steam generation performance by maximizing the absorption of sunlight, but great challenges in manipulation simplification and structure controllability still remain. Herein, a polyester (PET) fabric covered with a vertically aligned 3D tower-like ferrosoferric oxide (Fe3 O4 ) array via a convenient magnetically driven spray-coating method is reported, and both the spatial density and height of the Fe3 O4 array are tunable upon spraying time. It shows an extremely high solar absorbance (98.6%) in the entire solar spectrum, which is superior to the corresponding 2D Fe3 O4 structure (91.1%). Combining the obtained 3D Fe3 O4 /PET with a yolk-shell hydrophobic/superhydrophilic modified melamine-formaldehyde (mMF) sponge, the carefully designed and fabricated 3D Fe3 O4 /PET-mMF evaporator can realize a high water evaporation rate of 1.59 kg m-2 h-1 under 1 kW m-2 solar illumination, outperforming most related solar steam generation systems. With the advantages of cost-effectiveness, high evaporation rate, reliable endurance, and structural controllability, this 3D structural design provides an avenue to build up high-performance solar energy-driven water steam generation systems.


Morphological and molecular characterization of Isospora neochmiae n. sp. in a captive-bred red-browed finch (Neochmia temporalis) (Latham, 1802).
A new Isospora (Apicomplexa: Eimeriidae) species is described from a single red-browed finch (Neochmia temporalis) (subspecies N. temporalis temporalis), that was part of a captive population in Western Australia. Sporulated oocysts of this isolate are spherical, 18.3 (18.2-18.9) × 18.2 (18.2-18.6) μm, with a shape index (length/width) of 1.0; and a smooth and bilayered oocyst wall, 1.2 μm thick (outer layer 0.9 μm, inner 0.3 μm). A polar granule is present, but the oocyst residuum and a micropyle are absent. The sporocysts are ovoid-shaped, 13.3 (9.5-16.4) × 8.6 (6.8-10.0) μm, with a shape index of 1.5. An indistinct Stieda body is present, but the substieda body is absent. A sporocyst residuum is present and composed of numerous granules of different size scattered among the sporozoites. Morphologically, the oocysts from this isolate are different from those of all known valid Isospora spp. Molecular analysis was conducted at 4 loci; the 18S and 28S ribosomal RNA (rRNA), the mitochondrial cytochrome oxidase (COI) gene and the heat shock protein 70 (hsp70) gene. At the 18S locus, this new isolate exhibited 99.9%, 99.8%, 99.7%, and 99.5% similarity to I. sp. MAH-2013a from a superb starling (Lamprotornis superbus), I. MS-2003 from a Southern cape sparrow (Passer melanurus), I. sp. Tokyo from a domestic pigeon (Columba livia domestica) and I. MS-2003 from a Surinam crested oropendula (Psarocolius decumanus). At the 28S locus, this new isolate exhibited 99.7% similarity to both an Isospora sp (MS-2003) from a Northern house sparrow (Passer domesticus) and an Isospora sp. (MS-2003) from a Southern cape sparrow. At the COI locus, this new isolate exhibited 98.9% similarity to an Isospora sp. ex Apodemus flavicollis. At the hsp70 locus, this new isolate exhibited 99% similarity to isolate MS-2003 (AY283879) from a wattled starling (Creatophora cinerea). Based on morphological and molecular data, this isolate is a new species of Isospora, which is named Isospora neochmiae n. sp. after its host, the red-browed finch (Neochmia temporalis).


Role of cardiological specialistic evaluation in patients with chest pain presenting in the emergency department.
Aim of this study was to evaluate the impact of cardiological and echocardiographic evaluation in addition to a standard clinical and instrumental approach on diagnostic and prognostic accuracy in patients presenting in the emergency department (ED) with chest pain (CP). Acute coronary syndromes, pulmonary embolism and acute aortic syndromes (AAS) (triple-rule-out/TRO) were considered. From 7040 patients presenting with CP from 1 January 2015 to 31 December 2017, we randomly selected a sample of 1119. We retrospectively evaluated the clinical course and definitive diagnosis according to the ED final report. A 6-month follow-up to assess incident acute cardiovascular events was made by telephone interview in discharged patients; in hospitalized patients, clinical records were analyzed to evaluate the appropriateness of admissions. Diagnostic and prognostic accuracy wasd estimated through sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, according to the presence or absence of cardiological and echocardiographic consultation. Complete information of 1099 patients out of 1119 was retrieved. Seven hundred and eighty-eight patients (71.70%) had been discharged, eight inappropriately (0.73%). Three hundred eleven (28.30%) had been hospitalized, 14 (1.27%) inappropriately. Diagnostic performance showed 97.38% sensitivity, 98.24% specificity, 95.5% PPV and 99% NPV, with an overall accuracy of 98.00%. In patients evaluated by the cardiologist in addition to the ED physician (n = 387) we observed an improvement of sensitivity and NPV at the expense of specificity. Among improperly discharged patients, 7/8 had normal troponin, 7/8 normal ECG and only 1 was evaluated by a cardiologist. Only one inappropriately hospitalized patient was not evaluated by a cardiologist. Early consultation with a cardiologist and echocardiography improves clinical judgment in doubtful cases of CP, increasing diagnostic performance mainly by reducing inappropriate patient discharge and guaranteeing a low rate of inappropriate hospitalizations.


Satisfaction and perceived effectiveness in patients on subcutaneous immunotherapy with a high-dose hypoallergenic pollen extract.
This study was designed to determine the level of satisfaction, tolerance and perceived effectiveness by patients in the first pollen season after starting treatment with Alergovit(®). For this purpose, a nationwide, retrospective, multicentre and cross-sectional observational study was carried on 256 patients. Perceived effectiveness by the patients was measured using a visual analogue scale and was clinically significant in 92.4% of the patients. The satisfaction level was evaluated with a specific questionnaire. 32.5% of the patients were totally satisfied with Allergovit(®) and 48.8% reported a high degree of satisfaction. The treatment was well tolerated by 99.2% of the patients. Our results demonstrate that subcutaneous immunotherapy with Allergovit(®) is effective and well-tolerated in routine clinical practice.


Local proliferation of brain macrophages in central nervous system tissue cultures.
Mouse central nervous system tissue cultured for different lengths of time was analyzed for the proliferation of macrophages. These cells were identified and characterized by ultrastructural features, cell surface determinants and their ability to ingest latex particles and bacteria. Under the experimental conditions chosen brain macrophages were derived from perivascular cells which in short term cultures remained attached to blood vessels and later differentiated into brain macrophages with a typical ultrastructural appearance. Identical results were obtained when intravascular cells were largely removed by extensive saline perfusion before culturing. Macrophages assembled around stab wounds of the central nervous system or obtained from peritoneal lavage showed comparable cytological characteristics and cell membrane determinants.


Ethnic variation in fertility of Barpeta district: a demographic study.
"The present paper is aimed at investigating the ethnic differentials in respect of the effects of different socio-economic and demographic characteristics upon fertility among four major ethnic groups of people [in the Barpeta district of Assam, India]."


Computed tomography for the detection of free-floating thrombi in the right heart in acute pulmonary embolism.
The aim of this study was to assess the prevalence of free-floating thrombi in the right heart (FFT) and the accuracy of computed tomography (CT) for their detection in pulmonary embolism (PE). We studied 340 consecutive patients presenting with PE. All patients underwent CT and echocardiography. The prevalence of FFT was 3.5% in the global population of PE and 22% in high-risk PE. Dyspnoea, cardiogenic shock, cardiac arrest and tachycardia were more frequently found in patients with FFT (p = 0.04, p < 0.0001, p = 0.0003 and p = 0.01, respectively). Sensitivity and specificity of CT for the detection of FFT were 100% (95% confidence interval: 74%-100%) and 97% (95%-99%), whereas positive and negative predictive values were 57% (34%-78%) and 100% (99%-100%). Among patients with FFT, right ventricular dilation was always detected by CT, whereas no right ventricular dilation was found among patients with a false diagnosis of FFT performed by CT (p < 0.0001). Prevalence of FFT is 3.5% and differs according to the clinical presentation. Detection of FFT by CT is feasible and should lead to echocardiography being promptly performed for the confirmation of FFT.


Perceptions of vulnerability to a future outbreak: a study of horse managers affected by the first Australian equine influenza outbreak.
A growing body of work shows the benefits of applying social cognitive behavioural theory to investigate infection control and biosecurity practices. Protection motivation theory has been used to predict protective health behaviours. The theory outlines that a perception of a lack of vulnerability to a disease contributes to a reduced threat appraisal, which results in poorer motivation, and is linked to poorer compliance with advised health protective behaviours. This study, conducted following the first-ever outbreak of equine influenza in Australia in 2007, identified factors associated with horse managers' perceived vulnerability to a future equine influenza outbreak. Of the 200 respondents, 31.9% perceived themselves to be very vulnerable, 36.6% vulnerable and 31.4% not vulnerable to a future outbreak of equine influenza. Multivariable logistic regression modelling revealed that managers involved in horse racing and those on rural horse premises perceived themselves to have low levels of vulnerability. Managers of horse premises that experienced infection in their horses in 2007 and those seeking infection control information from specific sources reported increased levels of perceived vulnerability to a future outbreak. Different groups across the horse industry perceived differing levels of vulnerability to a future outbreak. Increased vulnerability contributes to favourable infection control behaviour and hence these findings are important for understanding uptake of recommended infection control measures. Future biosecurity communication strategies should be delivered through information sources suitable for the horse racing and rural sectors.


Bleomycin-induced pulmonary fibrosis in genetically mast cell-deficient WBB6F1-W/Wv mice and mechanism of the suppressive effect of tranilast, an antiallergic drug inhibiting mediator release from mast cells, on fibrosis.
It has been well known that the number of mast cells increases during the development of fibrosis in various tissues including the lung. However, the role of mast cells in fibrosis still remains obscure. In the present paper, we evidenced that pulmonary fibrosis could be induced in genetically mast cell-deficient WBB6F1-W/Wv mice as well as WBB6F1-(+/+) mice having mast cells normally by the treatment with bleomycin (BLM, 5 mg/kg, i.v., 10 days), and there was not much difference in the histological changes of lungs between the two strains. An increase in the hydroxyproline content of the lung of WBB6F1-W/Wv mice was rather higher than that of WBB6F1-(+/+) mice. Previously, we reported that tranilast, an antiallergic drug inhibiting chemical mediator release from mast cells, suppressed the development of BLM-induced pulmonary fibrosis in ICR mice, suggesting the possibility that mast cells play certain roles in fibrosis. However, it was evidenced in the present report that tranilast suppressed BLM-induced fibrosis in WBB6F1-W/Wv mice. Tranilast neither suppressed the cytotoxic activity of BLM against KB cells and L-929 cells in vitro, nor inhibited the antitumor activity of BLM against Sarcoma-180 transplanted subcutaneously into ICR mice. Tranilast may act through suppressing BLM-induced activation of lymphoid cells including macrophage and neutrophil. These results indicate an inconsequential role of mast cells in the development of fibrosis. Increases in the number of mast cells and in histamine content of the lung, which were widely reported in the lungs of BLM-treated mice, may be the result of fibrosis.


RXR isoforms and endogenous retinoids in the fiddler crab, Uca pugilator.
The pleiotropic effects of circulating ecdysteroids in the adult fiddler crab, Uca pugilator, during molting, regeneration, and reproduction are mediated by a limited number of receptor proteins. We hypothesize that hormonal effects in vivo may be the result of complex interactions between at least two receptor heterodimer conformations that differentially respond to multiple ecdysteroid/retinoid signals. Two splicing variants of the fiddler crab retinoid-X-receptor (UpRXR) differ from one another by the addition of a 33 amino acid insert in the ligand-binding domain. We show here that the ecdysteroid receptor in the fiddler crab (UpEcR) behaves differently depending upon the UpRXR isoform with which it is partnered. The two UpRXR variant partners for UpEcR confer slightly different responses in the binding of Ponasterone A (PA)-a naturally occurring ecdysteroid in the blood of Uca. UpRXR can bind 9-cis retinoic acid (9cRA) as well as terpenoids. 9cRA and the naturally occurring terpenoid, methyl farnesoate, influence the binding of PA to UpEcR/UpRXR dimers. Endogenous retinoids are found in the blastema of regenerating limbs of Uca and they (plus blood-borne terpenoids) may add additional levels of differential response by target tissues. Thus, the two sets of heterodimers tested here may represent different dynamic complexes whose properties are defined by the specific heterodimeric subunits involved and the specific ligands available.


Brain death: medical and legal issues.
Irreversible cessation of brain function has become a widely accepted criterion of death. Case law, state statutes, and medical opinion, backed by clinical studies, all support the use of brain death criteria as a means of determining death. Current state statutes are in need of some uniformity, as 12 different statutory approaches to brain death are currently in use. Brain death should not be confused with the still unresolved issue of termination of life support to terminally ill, mentally incompetent patients, or those who are comatose yet do not meet brain death criteria.


The efficacy of cytokine-induced killer cell infusion as an adjuvant therapy for postoperative hepatocellular carcinoma patients.
Even after surgery, hepatocellular carcinoma (HCC) has poor prognosis; adjuvant therapy is needed to improve effectively the outcome of HCC patients. We evaluated the efficacy of cytokine-induced killer (CIK) cell infusion as an adjuvant therapy for postoperative HCC patients. A total of 410 patients were studied retrospectively (January 2002 to January 2007): 206 received surgery alone; 204 received surgery and at least four cycles of CIK cell transfusion (CIK group). Kaplan-Meier and Cox regression analyses were used to explore differences in OS between two groups. The CIK group overall survival rates were significantly higher than that of the surgery-alone group (log-rank test; p = 0.0007). Multivariate survival analysis showed that CIK cell treatment was an independent prognostic factor. In subgroup analysis, patients who received ≥8 cycles of CIK cell transfusion exhibited significantly better survival than the <8 cycle group (p = 0.0272). There was no significant difference in overall survival in patients with ≤5-cm tumors between the CIK and surgery-alone groups (p = 0.7567). However, in patients with >5-cm tumors, the CIK group displayed significantly better overall survival than the surgery-alone group (p = 0.0002). Postoperative immunotherapy with CIK cell transfusion may be an effective adjuvant treatment for improving the outcomes of HCC patients; >8 cycles of CIK cell transfusion may ensure that patients derive maximal benefits. Moreover, patients with large tumors might benefit more from CIK cell adjuvant treatment than patients with small tumors.


Stereological estimation of orientation distribution of generalized cylinders from a unique 2D slice.
Though three-dimensional (3D) imaging gives deep insight into the inner structure of complex materials, the stereological analysis of 2D snapshots of material sections is still necessary for large-scale industrial applications for reasons related to time and cost constraints. In this paper, we propose an original framework to estimate the orientation distribution of generalized cylindrical structures from a single 2D section. Contrary to existing approaches, knowledge of the cylinder cross-section shape is not necessary. The only requirement is to know the area distribution of the cross-sections. The approach relies on minimization of a least squares criterion under linear equality and inequality constraints that can be solved with standard optimization solvers. It is evaluated on synthetic data, including simulated images, and is applied to experimental microscopy images of fibrous composite structures. The results show the relevance and capabilities of the approach though some limitations have been identified regarding sensitivity to deviations from the assumed model.


In vitro isolation and characterisation of a bovine Neospora species in Japan.
Eleven aborted bovine fetuses and five calves suspected as having neosporosis were necropsied and tissues from these animals were inoculated into bovine cardiopulmonary aortic endothelial cells and monkey kidney cells and maintained at 37 degrees C with 5 per cent CO2. Neospora tachyzoites were observed in one cell 49 days after inoculation. The isolated parasite (JPA1) was morphologically identical to the previously reported bovine Neospora species (BPA1) and confirmed by its strong antigenic reactivity with bovine control antisera to Neospora species and its lack of reactivity with Toxoplasma gondii and Sarcocystis cruzi antisera. This is the first bovine Neospora species isolate in Asia and further studies with this isolate are now expected.


Management of stage I testicular seminoma over a period of 49 years.
The aim of this study was to review the treatment, toxicity, and outcomes in patients with stage I seminoma after orchidectomy. A retrospective chart review of all patients with stage I seminoma referred for initial treatment during the last 49 years was performed. Initial treatment approaches, toxicity, and outcomes were analyzed. A total of 320 patients were seen between 1960 and 2009. Median age at diagnosis was 37 years (range: 20-72), with a median follow-up of 22.7 years (range: 1-48). All patients but 12 were treated with adjuvant radiotherapy. Acute toxicity was mainly gastrointestinal, with 7.6% classified as grade 2. The 10-year disease-specific survival and relapse-free survival were 97.7 and 97.6%, respectively. 8 patients (2.7%) developed a relapse and were managed with chemotherapy. 10 patients died, 6 of the disease and 4 from other causes (disease-free at time of death). In the management of stage I seminoma, 3 treatment options are available; currently in the European Consensus, surveillance is the first choice, considering the overall comparable outcome and the low acute and late toxicity. Adjuvant radiotherapy and adjuvant chemotherapy should be considered as alternative options only if the patient declines the surveillance strategy.


Assignment of aromatic resonances in the 1H nuclear magnetic resonance spectra of cardioactive polypeptides from sea anemones.
High-resolution 1H NMR spectroscopy at 300 MHz has been used to investigate the aromatic residues of a series of homologous polypeptides from sea anemones: anthopleurin-A from Anthopleura xanthogrammica and toxins I and II from Anemonia sulcata. Using two-dimensional NMR techniques, specific assignments to individual protons have been made for all aromatic resonances in the spectra of these molecules. In all three polypeptides the resonances from the two conserved Trp residues, 23 and 33, are shifted significantly from their random coil values, and the indole NH resonance of Trp-23 is not observed. These shift perturbations are due in part to a mutual interaction of the two indole rings, which is also indicated by the observation of nuclear Overhauser enhancements between protons of the two rings. Several other nonpolar side chains also interact with these two Trp residues, forming a hydrophobic region, the overall structure of which is conserved throughout the series. The other aromatic residues in these polypeptides appear not to participate in this structural region.


The effect of extraction of four second permanent molars on the incisor overbite.
Changes in incisor overbite were compared in 33 subjects who had four second molars extracted and 33 untreated subjects. There was an average increase in overbite of 0.7 mm in the extraction group, significantly different from an average decrease of -0.8 mm in the control group. The tendency to increase in overbite was greater in subjects whose presenting overbite was already reduced. The mechanism responsible for overbite reduction appeared to be a slight distal movement of the dentition, with retroclination of incisors and increase in inter-incisal angle.


Rearing in captivity affects spermatogenesis and sperm quality in greater amberjack, Seriola dumerili (Risso, 1810).
The greater amberjack, (Risso, 1810), is a promising candidate for the diversification of European aquaculture production, but inconsistent reproduction in captivity prevents commercial production. Recent studies showed that greater amberjack confined in sea cages exhibited scarce gonad development and early interruption of gametogenic activity during the reproductive season. The aim of the present study was to improve our understanding of the observed impairment of spermatogenesis. Adult wild and captive-reared males were sampled during 3 different phases of the reproductive cycle: early gametogenesis (EARLY; late April to early May), advanced gametogenesis (ADVANCED; late May to early June), and spawning (SPAWNING; late June to July). Spermatogonial stem cells and proliferating germ cells were identified through the immunohistochemical localization of and proliferating cell nuclear antigen, respectively. Apoptotic germ cells were identified throughout the terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labeling method. Sperm quality of captive-reared fish was evaluated using computer-assisted sperm analysis. Captive-reared males exhibited seminiferous lobules of a smaller diameter, a precocious and progressive decrease of spermatogonial mitosis, and a high level of apoptosis at the beginning of the reproductive season, concomitant with a many-fold higher 17β-estradiol plasma concentration. The motile spermatozoa percentage of captive greater amberjack was lower than in other teleosts, and a drastic decrease of spermatozoa motility duration, velocity, and ATP content occurred along the reproductive season. An abnormal increase of sperm concentration as well as an increase of dead spermatozoa occurred during the SPAWNING phase, probably because of lack of sperm hydration and ejaculation and consequent sperm ageing. The present study demonstrates the extreme susceptibility of greater amberjack to rearing stress and underscores the need for improvement of the rearing and handling procedures to ameliorate gametogenesis dysfunctions in commercial aquaculture production.


Integrated Analysis of DNA Repair Genes Identifies SLC6A1 as a New Marker for the Clinical Outcome of Patients with Colorectal Cancer.
Colorectal cancer (CRC) remains an important malignancy worldwide with poor prognosis. It has been known that DNA repair genes are involved in the development and progression of various tumors. Therefore, the purpose of this study was to explore DNA repair gene-based prognostic biomarkers for CRC. In this study, the expressing pattern and prognostic values of DNA repair genes in CRC patients were analyzed using TCGA database. GO and KEGG enrichment analyses were conducted to clarify the functional roles of dysregulated genes. We observed 358 differentially expressed DNA repair genes in CRC specimens, including 84 downregulated genes and 275 upregulated genes. 36 survival-related DNA repair genes were correlated with CRC patients' five-year survival, including 6 low-risk genes and 30 high-risk genes. Among the 10 overlapping genes, we focused on SLC6A1 which was highly expressed in CRC, and multivariate analysis confirmed that SLC6A1 expression as well as age and clinical stage could be regarded as an independent predicting factor for CRC prognosis. KEGG assays revealed that SLC6A1 may influence the clinical progression via regulating TGF-beta and PI3K-Akt signaling pathways. In addition, we observed that SLC6A1 was negatively regulated by SLC6A1 methylation, leading to its low expression in CRC specimens. Overall, SLC6A1 is upexpressed in CRC and can be used as a marker of poor prognosis in CRC patients.


Novel actin-related proteins Arp-T1 and Arp-T2 as components of the cytoskeletal calyx of the mammalian sperm head.
The calyx is a large cytoskeletal component of the perinuclear theca of the mammalian sperm head, displaying remarkable morphological interspecies differences, which is biochemically characterized by resistance to high ionic strength and detergents and by a special protein composition, including the basic proteins calicin, cylicin I and II, and two major actin-capping proteins. In our calyx preparations from bull spermatozoa we have noted two major acidic components which upon partial amino acid sequencing have been identified as novel members of the subfamily of actin-related proteins (Arps). Antibodies raised against the corresponding human proteins, termed Arp-T1 and Arp-T2, have been used to detect the proteins by immunoblotting and immunofluorescence microscopy, demonstrating their specific synthesis in the testis, late in spermatid differentiation, and their localization in the calyx. The discovery of two novel Arps as major components in a cytoskeletal, nonmotile structure of mammalian spermatozoa suggests that certain members of this family of proteins may serve functions other than nucleation of actin filaments, and possible biological roles of such Arps in spermatozoa are discussed.


Percent body fat is a risk factor for relapse in anorexia nervosa: a replication study.
We aimed to replicate and extend our previous findings of an association between percent body fat in recently weight-restored patients with Anorexia Nervosa (AN) and clinical outcome in the year following treatment. Twenty-two hospitalized, weight-restored women with AN underwent whole body MRI to determine percent adipose tissue. Following hospital discharge, patients were contacted regularly, and at the end of the year, clinical outcome was determined using modified Morgan-Russell (MR) criteria: full, good, fair or poor. Identical to our previous study, outcome was dichotomized into "full, good or fair" and "poor" groups. Data from 21 subjects were available for analysis. Percent body fat was significantly lower in the poor outcome group (22% ± 5%) compared to the "full, good or fair" outcome group (27 % ± 4%)(p < 0.035). To further examine the relationship, we combined data from the current study with data from the 26 subjects on whom we had previously reported. Univariate analysis of variance (ANOVA) demonstrated a significant difference in percent adipose tissue across the four MR outcome groups (F = 3.416, df = 3, p<0.03). Lower percent adipose tissue after short-term weight normalization is associated with poor clinical outcome in the year following inpatient treatment. These findings may be important in the assessment of risk for relapse in patients with AN.


The isolation and characterization of linked delta- and beta-globin genes from a cloned library of human DNA.
A cloned library of large, random embryonic human DNA fragments was constructed and screened for beta-globin sequences using the cloned human beta-globin cDNA plasmid pJW102 (Wilson et al., 1978) as a hybridization probe. Two independent clones were obtained and then characterized by restriction endonuclease cleavage analysis, hybridization experiments and partial DNA sequencing. Each of the clones carries both the adult delta- and beta-globin genes. The two genes are separated by approximately 5.4 kilobases (kb) of DNA and their orientation with respect to the direction of transcription is 5'-delta--beta-3'. Both the delta- and beta-globin genes contain a large noncoding intervening sequence (950 and 900 bp, respectively) located between the codons for amino acids 104 (arginine) and 105 (leucine). Although the location of the large intervening sequence within the coding regions of the two genes is identical, the two noncoding sequences bear little sequence homology. A second, smaller intervening sequence similar to that found in other mammalian beta-globin genes was detected near the 5' end of the human beta-globin gene. The two independently isolated beta-globin clones differ from each other by the presence of a Pst I restriction enzyme cleavage site within the large intervening sequence of the delta-globin gene of one of the clones. This suggests that the human DNA carried in the two clones was derived from two homologous chromosomes which were heterozygous for the Pst I restriction enzyme recognition sequence.


Size-exclusion chromatography selective cleanup of aflatoxins in oilseeds followed by HPLC determination to assess the potential health risk.
Aflatoxins (AFs) are one of the most harmful carcinogenic natural toxins that affect food. Crops containing reasonably high oil content may be affected by Aspergillus species and consequently by AF contamination. In this study, a proposed testing method for AF detection in oilseed was developed, validated, and used for a market survey to assess the probabilistic risk exposure caused by consuming contaminated oilseeds including corn, sunflower seed, and soybean. The test method was optimized for selective extraction and then validated for fitness of purpose; the limits of quantification (LOQs) were 0.2, 0.4, 0.2, and 0.2 μg kg-1 for aflatoxin G1 (AFG1), aflatoxin B1 (AFB1), aflatoxin G2 (AFG2), and aflatoxin B2 (AFB2), respectively. The method was linear from the LOQs up to 20 μg kg-1, and its budget of measurement uncertainties were estimated at 25, 24, 26, and 30 for AFG1, AFB1, AFG2, and AFB2, respectively. The contamination levels were from <LOQ to 2.65 μg kg-1 and from <LOQ to 26.9 μg kg-1 for corn and sunflower oilseed samples, respectively, whereas the soybean samples were AF-free. According to the consumption rate of corn and sunflower seeds, the estimated margins of exposure to AFB1 were 721 and > 10,000 body weight (BW) day-1, respectively. The main finding of the present study highlights the possibility of some risk of AF exposure from corn consumption, which may represent a health concern.


The role of insulin 3, testosterone, Müllerian inhibiting substance and relaxin in rat gubernacular growth.
Transabdominal testicular descent is influenced by various anatomical and hormonal factors and is mediated by gubernacular enlargement and regression of the cranial suspensory ligament, but its mechanism remains controversial. The aim of this study was to determine which hormones have a direct effect on the proliferation of cells in the day 17 fetal rat gubernaculum in vitro, using an organ culture system. The effects of synthetic rat insulin 3 (INSL3), inactive INSL3, dihydrotestosterone (DHT), DHT+INSL3, human Müllerian inhibiting substance (hMIS), hMIS+INSL3 and human gene 2 relaxin were tested, together with co-culture with fetal rat testis. Cell proliferation was assessed using a bromodeoxyuridine labelling index. The results showed that MIS and relaxin have a mild effect on gubernacular growth, whilst INSL3 and DHT have a more marked effect. The combination of MIS+INSL3 showed an effect close to that of co-culture with testis. However, the most pronounced effect was caused by DHT+INSL3. RT-PCR analysis indicated that the fetal rat gubernaculum strongly expresses putative INSL3 receptors, weakly expresses MIS type II receptors and does not express relaxin receptors. In conclusion, a number of different hormones directly influence growth of the gubernaculum in vitro, including the recently reported hormone INSL3. INSL3 shows a direct stimulatory effect on the swelling reaction, while DHT and MIS may have roles in augmenting this growth.


The avermectin/milbemycin receptors of parasitic nematodes.
Glutamate-gated chloride channels are the most important target of ivermectin and related compounds in parasitic nematodes. A small family of genes encode subunits of these channels, allowing the assembly of multiple channel subtypes; the subunit composition of most of the native receptors is unknown. The members of the gene family vary between species, making extrapolation from C. elegans to parasites difficult. Expression of recombinant receptors in Xenopus oocytes can identify subunits that have the ability to co-assemble into novel channels, but localisation data, ideally at the single-cell level, is required to confirm that these subunits are expressed in the same cells and tissues. Fortunately, recent advances in this area are starting to make this information available; this information is adding to our understanding of how the drugs act and of the possible subunit combinations that create their targets in vivo.


[The reproduction of families affected by Steinert's dystrophy in Saguenay (Quebec), 1885-1971: demographic parameters].
"In the light of the literature in the field, one would expect that the myotonic dystrophy (or Steinert) gene carries a severe selective disadvantage. Indeed, this phenotype is commonly said to entail...sterility, infant mortality, and a lower nuptiality. In the worst cases, it is not unlikely that the gene could eliminate itself through non-reproduction. [A model is developed and] tested in the Saguenay (Quebec) population, known for its exceptionally high prevelance (1/475) of the disease. Authors have been able to use a computerized demographic and genealogical data base in order to study several demographic variables (fertility, nuptiality, mortality, etc)....Case-control analyses produced very [few] differences between affected and control families, suggesting no significant selective disadvantage associated with the gene." (SUMMARY IN ENG AND ITA)


Impact of a decline in Colorado Medicaid managed care enrollment on access and quality of preventive primary care services.
Beginning in 1997 the Colorado Medicaid program de-emphasized managed care and shifted children from enrollment in a health maintenance organization (HMO), which required an enrollee to have an assigned primary care physician, to either the unassigned fee-for-service (UFFS) program in which the enrollee was not required to have a primary care physician (PCP) or to the primary care physician program (PCPP) in which the enrollee was required to select a participating PCP if one was available. The proportion of Medicaid enrollee-months in HMOs dropped from 75.4% in 1997 to 29% in 2003, whereas the proportion of enrollee-months in UFFS programs during this time period increased from 18.6% to 45.6%, and the proportion in the PCPP increased from 5.5% to 25.3%. This shift of children from HMO managed care to the UFFS program provided a natural experiment to assess the impact of not having an assigned PCP on pediatric primary care services. We sought to assess whether an elective shift of children from Medicaid HMO managed care plans with an assigned PCP to the UFFS program without an assigned PCP restricted access to a primary care medical home, recommended health supervision visits, and age-appropriate immunizations. Published Colorado Health Plan Employer Data and Information Set (HEDIS) data for 1999-2003 were reviewed to determine if Colorado children enrolled in Medicaid managed care programs with an assigned PCP (HMO and PCPP) compared with the UFFS program were more likely to have any type of visit with a PCP, to have recommended health supervision visits, and to be fully immunized. In the analysis, "HMO total" refers to the average of all children participating in HMO plans. Kaiser Permanente was considered a benchmark because it had the highest immunization rates of all HMOs. "Total Colorado" refers to the average of all children enrolled in Medicaid including the managed care and UFFS options. For 2-year-olds, the 4:3:2:1:1 combination immunization included 4 diphtheria-tetanus-acellular pertussis vaccines, 3 oral poliovirus vaccines or inactivated polio vaccines, 2 hepatitis B vaccines, 1 Haemophilus influenzae type b vaccine, and 1 measles-mumps-rubella vaccine. In 1999 the percentages of children 12 to 24 months of age having any type of visit with a PCP were >80% for the PCPP, Kaiser Permanente, and UFFS programs. However, although the proportion with any visit remained >85% in 2001 for children enrolled in the PCPP and Kaiser Permanente program, the percentage dropped 13.9% to 66.2% for children in the UFFS program. In 2001 the percentage of children with any type of PCP visit enrolled in the UFFS program (66.2%) was significantly lower than the total Colorado (73.6%) as well as the PCPP (85.7%) and Kaiser Permanente program (97.7%). Children 12 to 24 months of age enrolled in the PCPP in 2001 were 1.3 times more likely to have any type of visit with a PCP compared with those enrolled in the UFFS program. Children in the PCPP in 2001, 2002, and 2003 were 1.4, 1.9, and 2.6 times more likely, respectively, to have all 6 of the recommended health supervision visits compared with children enrolled in the UFFS program. Children 3 to 6 years old in the PCPP in 2001, 2002, and 2003 were 1.3, 1.5, and 1.4 times more likely, respectively, to have an annual health supervision visit compared with children enrolled in the UFFS program. In 1999, 2001, 2002, and 2003 2-year-old children enrolled in the PCPP were 2.0, 1.4, 1.5, and 1.8 times more likely, respectively, to be up-to-date with 4:3:2:1:1 vaccines compared with children enrolled in the UFFS program. In 1999, 2001, 2002, and 2003 adolescents enrolled in the PCPP were 1.8, 1.6, 1.3, and 1.6 times more likely, respectively, to be up-to-date with 2 measles-mumps-rubella vaccines compared with children enrolled in the UFFS program. This study documents the diminishing ability of the Colorado Medicaid program to provide children access to the benefits of a medical home, including visits with PCPs, recommended health supervision visits, and immunizations as care was shifted to the UFFS program from HMO managed care. The high up-to-date immunization rates achieved by Kaiser Permanente suggest that differences in immunization rates reflect the effectiveness of the care processes rather than the characteristics of the Medicaid population.


T cell development in CD3-zeta mutant mice.
Increasing evidence points to multiple pathways of T lymphocyte development. The well characterized thymus-dependent pathway gives rise to T cells bearing TCR alpha beta heterodimers and either CD4 or CD8 alpha beta co-receptors. T cells of this lineage populate peripheral lymphoid compartments including lymph nodes, spleen, skin, and Peyer's patches. By comparison, factors which govern extrathymic T cell development are poorly understood. A variety of experiments have shown that intestinal intraepithelial lymphocytes (IELs) develop outside of the thymic environment, e.g., in the gut of nude, SCID, and beta 2m-/- mutant mice, and after transplanting bone marrow or fetal liver cells into irradiated thymectomized adult mice. This review focuses on the role of the CD3-zeta subunit in the development of both thymically and extrathymically derived T cells as determined by gene-targeting experiments in mice. Data from these and other T cell-related mutations continue to define crucial stages in thymocyte differentiation. Most interestingly, CD3-zeta mutant mice contain a unique population of intestinal IELs that develops independently of thymic selective processes and expresses a novel TCR/CD3 complex.


Stress and poverty predictors of treatment adherence among people with low-literacy living with HIV/AIDS.
To examine the association of social, health, and poverty-related stressors in relation to antiretroviral therapy adherence in a sample of people with low-literacy living with HIV/AIDS in the southeastern United States. Emotional distress is among the more common factors associated with HIV treatment adherence. Typical barriers to adherence may be overshadowed by poverty experiences in the most disadvantaged populations of people living with HIV/AIDS, such as people with lower-literacy skills. One hundred eighty-eight men and women living with HIV/AIDS who demonstrated poor health literacy completed measures of social and health-related stress, indicators of extreme poverty, as well as other factors associated with nonadherence. HIV treatment adherence was monitored prospectively, using unannounced pill counts. Two-thirds of the sample demonstrated adherence <85% of pills taken. Multivariable analyses showed that food insufficiency and hunger predicted antiretroviral therapy nonadherence over and above depression, internalized stigma, substance use, and HIV-related social stressors. Interventions for HIV treatment nonadherence with the most socially disadvantaged persons in developed countries should be reconceptualized to directly address poverty, especially food insufficiency and hunger, as both a moral and public health imperative.


Role of neurotrophin signalling in the differentiation of neurons from dorsal root ganglia and sympathetic ganglia.
Manipulation of neurotrophin (NT) signalling by administration or depletion of NTs, by transgenic overexpression or by deletion of genes coding for NTs and their receptors has demonstrated the importance of NT signalling for the survival and differentiation of neurons in sympathetic and dorsal root ganglia (DRG). Combination with mutation of the proapoptotic Bax gene allows the separation of survival and differentiation effects. These studies together with cell culture analysis suggest that NT signalling directly regulates the differentiation of neuron subpopulations and their integration into neural networks. The high-affinity NT receptors trkA, trkB and trkC are restricted to subpopulations of mature neurons, whereas their expression at early developmental stages largely overlaps. trkC is expressed throughout sympathetic ganglia and DRG early after ganglion formation but becomes restricted to small neuron subpopulations during embryogenesis when trkA is turned on. The temporal relationship between trkA and trkC expression is conserved between sympathetic ganglia and DRG. In DRG, NGF signalling is required not only for survival, but also for the differentiation of nociceptors. Expression of neuropeptides calcitonin gene-related peptide and substance P, which specify peptidergic nociceptors, depends on nerve growth factor (NGF) signalling. ret expression indicative of non-peptidergic nociceptors is also promoted by the NGF-signalling pathway. Regulation of TRP channels by NGF signalling might specify the temperature sensitivity of afferent neurons embryonically. The manipulation of NGF levels "tunes" heat sensitivity in nociceptors at postnatal and adult stages. Brain-derived neurotrophic factor signalling is required for subpopulations of DRG neurons that are not fully characterized; it affects mechanical sensitivity in slowly adapting, low-threshold mechanoreceptors and might involve the regulation of DEG/ENaC ion channels. NT3 signalling is required for the generation and survival of various DRG neuron classes, in particular proprioceptors. Its importance for peripheral projections and central connectivity of proprioceptors demonstrates the significance of NT signalling for integrating responsive neurons in neural networks. The molecular targets of NT3 signalling in proprioceptor differentiation remain to be characterized. In sympathetic ganglia, NGF signalling regulates dendritic development and axonal projections. Its role in the specification of other neuronal properties is less well analysed. In vitro analysis suggests the involvement of NT signalling in the choice between the noradrenergic and cholinergic transmitter phenotype, in the expression of various classes of ion channels and for target connectivity. In vivo analysis is required to show the degree to which NT signalling regulates these sympathetic neuron properties in developing embryos and postnatally.


Barriers impeding serologic screening for celiac disease in clinically high-prevalence populations.
Celiac disease is present in ~1% of the general population in the United States and Europe. Despite the availability of inexpensive serologic screening tests, ~85% of individuals with celiac disease remain undiagnosed and there is an average delay in diagnosis of symptomatic individuals with celiac disease that ranges from ~5.8-11 years. This delay is often attributed to the use of a case-based approach for detection rather than general population screening for celiac disease, and deficiencies at the level of health care professionals. This study aimed to assess if patient-centered barriers have a role in impeding serologic screening for celiac disease in individuals from populations that are clinically at an increased risk for celiac disease. 119 adults meeting study inclusion criteria for being at a higher risk for celiac disease were recruited from the general population. Participants completed a survey/questionnaire at the William K. Warren Medical Research Center for Celiac Disease that addressed demographic information, celiac disease related symptoms (gastrointestinal and extraintestinal), family history, co-morbid diseases and conditions associated with celiac disease, and patient-centered barriers to screening for celiac disease. All participants underwent serologic screening for celiac disease using the IgA tissue transglutaminase antibody (IgA tTG) and, if positive, testing for IgA anti-endomysial antibody (IgA EMA) as a confirmatory test. Two barriers to serologic testing were significant across the participant pool. These were participants not knowing they were at risk for celiac disease before learning of the study, and participants not knowing where to get tested for celiac disease. Among participants with incomes less than $25,000/year and those less than the median age, not having a doctor to order the test was a significant barrier, and this strongly correlated with not having health insurance. Symptoms and co-morbid conditions were similar among those whose IgA tTG were negative and those who tested positive. There are significant patient-centered barriers that impede serologic screening and contribute to the delayed detection and diagnosis of celiac disease. These barriers may be lessened by greater education of the public and health care professionals about celiac disease symptoms, risk factors, and serologic testing.


Targeted Discovery of Pentaketide Ansamycin Aminoansamycins A-G.
Ansamycins are a class of macrolactams with diverse bioactivities, characterized by the unique 3-amino-5-hydroxybenzoic acid moiety. In this study, the ansamycin gene cluster aas in Streptomyces sp. S35 was activated by the constitutive coexpression of two pathway-specific regulator genes aas1 and aas10, and seven novel pentaketide ansamycin aminoansamycins A-G (1-7) were identified. Compound 4 with better antiproliferative activity indicated that the anthranilate analogues are probably promising building blocks for the production of unnatural ansamycins with improved activity.


The need for public education on HPV and cervical cancer prevention in Asia. Opinions of experts at the AOGIN conference.
Asia accounts for more than half of all cases of cervical cancer registered globally and improving prevention is urgently needed. A range of tools and strategies is now available to effectively prevent this disease, including two new prophylactic HPV vaccines approved and recommended for adolescents and young women. However, without communication these tools may have little impact on disease burden. The conferences of the Asia Oceania Research Organisation in Genital Infection and Neoplasia (AOGIN) bring together clinicians and scientists whose work is related to genital infections, particularly HPV, cervical dysplasia and neoplasia, as well as other anogenital cancers, with the aim of improving communication on prevention through human papillomavirus (HPV) vaccination and screening in Asian countries. The scope of this year's AOGIN conference was to extend education to include health workers, family doctors, paediatricians, governmental health agencies, and the general public through patients' testimonials that can reach out to women raising awareness of this silent disease. Community based initiatives and awareness campaigns were also reported, and can empower the people to engage in a dialog with local governments towards prioritization of cancer prevention programs, achieving more for the public than isolated actions. Parents and teachers are encouraged to communicate about these issues within families and schools. Evidence was discussed that males can participate in cervical cancer control as well, and prevention programs involving men should not be neglected as they may reduce genital disease burden in women. Opinion leaders proposed prevention measures to be considered for governmental decisions. While each country develops a locally appropriate policy for cervical cancer control there is a need to revise these programs regularly, as knowledge increases in response to public need, as well as to gather evidence about disease burden and the effectiveness of education and interventions. In conclusion, AOGIN is committed to improve communication with patients, health authorities, professional organizations and opinion leaders towards strengthening cervical cancer prevention in Asia, to achieve a timely steep reduction in this cancer.


PdCl2(HNMe2)2-catalyzed highly selective cross [2 + 2 + 2] cyclization of alkynoates and alkenes under molecular oxygen.
In the course of our study on palladium-catalyzed aerobic oxidation synthesis, we found that the PdCl(2)/O(2)/DMF system consistently experienced DMF hydrolysis to afford PdCl(2)(HNMe(2))(2), which is the real active catalyst for the aerobic oxidation. Although in situ DMF hydrolysis has been widely used in generating supramolecular assembly architectures, as far as we know, it is the first successful example to utilize PdCl(2)(HNMe(2))(2) in synthetic reactions. The highly selective cross [2 + 2+2] cyclization of alkynoates and different alkenes with electron-withdrawing groups could be smoothly catalyzed by PdCl(2)(HNMe(2))(2)/O(2)/DMF to afford the corresponding functionalized pentasubstituted benzenes in good to excellent yields (70-97%). The extension of alkyne surrogates for cross [2 + 2 + 2] cyclization from special alkenes with leaving groups to simple alkenes under molecular oxygen led to a paradigm shift in arene synthesis.


Copper toxicosis with hemolysis and hemoglobinuric nephrosis in three adult Boer goats.
Acute and, particularly, chronic copper exposures, along with defects in hepatic copper metabolism, altered excretion of copper, and/or nutritional imbalances between copper and other trace elements, can lead to hepatic accumulation of copper and primary copper toxicosis. There is interspecies variation in susceptibility to copper toxicosis, with sheep being the species most likely to develop this condition. Adult dairy goats and Boer crosses are generally considered resistant to chronic copper toxicosis, especially the hemolytic stage of this disease. The current report is rather unusual in that it describes instances of naturally occurring copper toxicosis with hemolysis and hemoglobinuric nephrosis in 3 adult Boer goats. In 2 of these goats, a possible source of excessive dietary copper was investigated but not definitively identified. In the third goat, the etiologic factors associated with the copper toxicosis were not determined. It appears that mature Boer goats are susceptible to the hemolytic stage of chronic copper toxicosis, which was not observed in a recent, large-scale copper intoxication involving lactating dairy goats. Copper analyses on both liver and kidney samples were necessary to confirm the diagnosis of copper toxicosis in all 3 goats. All feedstuffs associated with instances of copper toxicosis should be analyzed for iron, molybdenum, sulphur, and zinc as well as copper to determine what nutritional factors are contributing to the pathogenesis of this disease. Consideration also should be given to the ingestion of hepatotoxic plants and other toxic exposures, which could predispose an animal to secondary chronic copper toxicosis.


When full insurance may not be optimal: The case of restricted substitution.
Even when heavily subsidized, a substantial portion of people choose to forgo purchasing health insurance coverage. In this note, I introduce an explanation for this phenomenon which does not assume choice errors, incorrect beliefs, differently priced uncompensated care, or information asymmetries. When individuals are incapable of freely trading off health and wealth and the initial allocation of goods is suboptimal from their perspective, the standard result of demand for actuarially fair insurance in a single good world does not generalize to the health insurance context. Thus, people might not purchase full health insurance coverage even if it is priced at actuarially fair levels. I argue that this situation is particularly likely to occur in the low-income population, and hence it is relevant for the achievement of universal health coverage.


Spontaneous regression of congenital cutaneous hemangiomas in a calf.
Congenital vascular tumors of the skin have been described in people and a few animals, but unlike infantile hemangiomas in children, spontaneous regression has not been described in animals. A 2-day-old male Belgian Blue cross calf was presented for multiple congenital cutaneous masses that were soft, alopecic, and hyperemic; the calf had no other apparent abnormalities. Two weeks later, one mass had regressed. Surgical excision of one of the remaining masses was performed; histopathologic and immunohistochemical findings were considered diagnostic for epithelioid hemangioma. Eight months following initial presentation, all the masses had regressed spontaneously. This constitutes the first account in the veterinary literature of spontaneous regression in a congenital vascular tumor.


Comprehension and production of noun compounds by Estonian children with specific language impairment.
The authors examined how 12 Estonian-speaking children with specific language impairment (SLI) and 60 children with normal speech development (ND) comprehended compound nouns with differing sequence of the components (first task) and how they produced compound nouns to label genuine and accidental categories by using analogy (second task) and sentence transformation (third task). The results demonstrated that children with SLI were capable of producing compound nouns for genuine categories, but avoided production of compounds to label objects in temporary juxtapositions. However, by comparison with the control group, SLI children differed statistically significantly in terms of both the number of correct answers and the pattern of mistakes. In the cases when compound nouns were expected to be produced by transforming sentences, the results of SLI children were considerably lower than those of their peers. The results of this study support the idea that children with SLI experience difficulties related to processing linguistic information.


Resistance to extinction of conditioned electrodermal responses: a study of the incubation fear hypothesis.
In the present study we examined Eysenck's incubation hypothesis of fear. Probability of skin conductance response (SCR) was analyzed for a sample of 79 undergraduate women, ranging in age from 18 to 25 years. Different groups of participants were conditioned to two levels of unconditioned stimuli (UCS) intensity and presented to three levels of unreinforced conditioned stimuli (CS) exposures (extinction phase) in a delay differential conditioning paradigm. The CSs were fear-relevant slides (snakes and spiders) and the UCSs were aversive tones. Analysis did not show a clear incubation effect; instead an increased resistance to extinction of SCR probability in association to the high-UCS and the short unreinforced CS presentation was evident. Findings support partially Eysenck's incubation theory of fear/anxiety.


Effect of electrical and chemical stimulation of the lateral hypothalamus on taste preferences.
Bipolar stainless steel electrodes or stainless steel cannulas were implanted stereotaxically into the lateral hypothalamus of rats. Drinking was elicited by electrical or chemical (carbachol or angiotensin II) stimulation of animals, which were offered water and solutions of sodium chloride, saccharin, acetic acid and quinine. During electrical stimulation, ingestion of water and of all the solutions increased significantly. The same rats ingested significantly more sodium chloride and saccharin solution after 23 h water deprivation and electrical stimulation of the lateral hypothalamus. Carbachol administered into the lateral hypothalamus induced ingestion of saccharin solution and water but not of sodium chloride. Angiotensin II injected into the lateral hypothalamus did not induce drinking in most of the rats and those which drank preferred sodium chloride, saccharin and water. Several of the rats which did not respond to angiotensin II injection into the lateral hypothalamus, 72 h after angiotensin II responded to injection of carbachol by drinking the saccharin solution. The results of electrical stimulation suggest that the lateral hypothalamus consists of neurons involved in the ingestion of primary taste solutions. Depending on the functional state of the organism, lateral hypothalamic stimulation modifies ingestion of other taste substances but not of salt, as indicated by water deprivation. Chemical stimulation indicates that the neurotransmitter responsible for salt intake is not cholinergic and that the cholinergic neurons evoke preference for sweet taste and water. It appears that angiotensin II is involved in salt intake, as well as in producing preference for sweet taste and water.


Acceptability of the human papillomavirus vaccine in schools in Lusaka in Zambia: Role of community and formal health system factors.
Zambia has one of the highest cervical cancer rates in the world. This paper explores the acceptability of the Human Papillomavirus vaccine administered in girls (9-13 years) in Zambia. A qualitative case study was conducted in two schools in Lusaka district, which participated in the pilot for the Human Papillomavirus vaccine rollout. The study revealed that community level health systems factors such as knowledge levels about the vaccine, sexual morality concerns, conflicting views from parents on the vaccine, rumours that the vaccine contained cervical cancer and that it causes infertility in girls, previous bad experience with other vaccines, religious beliefs such as belief that God protects against illness, the nature of the school environment as well as faith in doctors shaped the uptake of the vaccine. Furthermore, formal health system factors such as availability of health workers and nature of collaboration between the Ministries of Health and Education influenced acceptability of the vaccine among the girls. Strengthening collaboration between community and formal health systems can play a vital role in supporting uptake of vaccines at community level as factors that hinder uptake of the vaccines emanate from both the community and health sector.


Neurofunctional Components of Simple Calculation: A Magnetoencephalography Study.
Our ability to calculate implies more than the sole retrieval of the correct solution. Essential processes for simple calculation are related to the spreading of activation through arithmetic memory networks. There is behavioral and electrophysiological evidence for these mechanisms. Their brain location is, however, still uncertain. Here, we measured magnetoencephalographic brain activity during the verification of simple multiplication problems. Following the operands, the solutions to verify could be preactivated correct solutions, preactivated table-related incorrect solutions, or unrelated incorrect solutions. Brain source estimation, based on these event-related fields, revealed 3 main brain networks involved in simple calculation: 1) bilateral inferior frontal areas mainly activated in response to correct, matching solutions; 2) a left-lateralized frontoparietal network activated in response to incorrect table-related solutions; and (3) a strikingly similar frontoparietal network in the opposite hemisphere activated in response to unrelated solutions. Directional functional connectivity analyses revealed a bidirectional causal loop between left parietal and frontal areas for table-related solutions, with frontal areas explaining the resolution of arithmetic competition behaviorally. Hence, this study isolated at least 3 neurofunctional networks orchestrated between hemispheres during calculation.


Disease mapping in veterinary epidemiology: a Bayesian geostatistical approach.
Model-based geostatistics and Bayesian approaches are useful in the context of veterinary epidemiology when point data have been collected by appropriate study design. We take advantage of an example of Epidemiological Surveillance on urban settings where a two-stage sampling design with first stage transects is applied to study the risk of dog parasite infection in the city of Naples, 2004-2005. We specified Bayesian Gaussian spatial exponential models and Bayesian kriging were performed to predict the continuous risk surface of parasite infection on the study region. We compared the results with those obtained by the application of hierarchical Bayesian models on areal data (proportion of positive specimens by transect). The models results were consistent with each other and the Bayesian geostatistical approach proved to be more accurate in identifying areas at risk of zoonotic parasitic diseases. In general, larger risk areas were identified at the city border where wild dogs mixed with domestic dogs and human or urban barriers were less present.


Chemoprevention by difluoromethylornithine: correlation of an in vitro human cell assay with human clinical data for biomarker modulation.
The efficacy of difluoromethylornithine (DFMO) as a chemopreventive agent has been tested in vitro using a human epidermal cell (HEC) assay with growth inhibition and involucrin induction as endpoints. Suppression of polyamine content is currently being utilized as a biomarker in clinical trials for the chemopreventive efficacy of DFMO against colon cancer formation. We have now examined the effects of DFMO on suppression of polyamine content in the HEC assay. The findings indicate 1) the % change in spermidine to spermine ratio and the depletion of putrescine show excellent correlation with chemopreventive efficacy in vitro; 2) the effective concentrations in vitro overlap the plasma concentrations in the clinical trial. These observations serve as further validation of the usefulness of the HEC assay as a screen for chemopreventive efficacy.


Vas deferens anomalies in paediatric age.
Vas deferens anomalies have been observed with high incidence in cystic fibrosis patients, whereas the overall incidence in the general population is estimated less than 0.05%. Vas deferens anomalies are sometimes associated with renal abnormalities and they are due to a damage occurring within the first weeks of gestational age. In other cases they can be the expression of a mild form of cystic fibrosis. The authors report on 7 patients with 10 anomalies of vas deferens: 2 patients with cystic fibrosis; 3 patients with urinary tract anomalies; 2 patients with no evidence of cystic fibrosis and without urinary tract anomalies. It is suggested that every patient presenting with vas deferens anomalies and no evidence of cystic fibrosis should be further evaluated with renal ultrasound; moreover all patients without evidence of both cystic fibrosis and renal anomalies should have genetic investigations.


Requirement of endogenous basic fibroblast growth factor for sensitization to amphetamine.
Repeated exposure to amphetamine produces long-lasting increases in sensitivity to its effects. We reported previously that repeated amphetamine treatment results in increased astrocytic expression of basic fibroblast growth factor (bFGF) in the ventral tegmental area (VTA) and substantia nigra compacta (SNc) and that this effect is prevented by coadministration of a nonspecific glutamate receptor antagonist. Here we show that the development of sensitization to amphetamine is prevented when amphetamine injections are preceded by infusions of a neutralizing antibody to bFGF into the VTA. In addition, we show that astrocytic bFGF expression is increased in the VTA and SNc of animals that exhibit behavioral sensitization and that the number of bFGF-immunoreactive astrocytes in these regions is strongly and positively correlated with the magnitude of sensitization. Cotreatment with an NMDA glutamate receptor antagonist blocks both the development of behavioral sensitization and bFGF induction. These results show that endogenous bFGF is necessary for the development of sensitization to amphetamine and suggest that bFGF mediates the glutamatergic-dopaminergic interaction that initiates the long-term consequences of repeated drug use.