Characterization of porcine endogenous retrovirus expression in neonatal and adult pig pancreatic islets.
Pig islets represent an alternative to the current modes of treatment for patients with diabetes. However, the concerns over pathogen transmission including that of PERV limit their immediate, widespread usage in humans. It has been previously demonstrated that PERV copy number and particularly expression levels can vary considerably between individuals and within different tissues of a single animal. In general, expression levels have been found to be particularly low in the pancreas compared to other porcine tissues suggesting a reduced risk associated with the use of this tissue. Data regarding this crucial aspect, however, remain limited and little is known about PERV status of islets themselves, which represent the final product to be transplanted. In addition, comparative analysis of the PERV status of neonatal piglets with adults is important as they are increasingly considered as potential islet donors for xenotransplantation. Tissue samples from 51 neonatal piglets (age between 14 and 21 days) and 29 adult pigs were collected from Belgian landrace pigs used for pancreas procurement and islet isolation. Tissue biopsies were used to extract DNA for PERV copy number quantification by qPCR and RNA for PERV expression by qRT-PCR. As expected, PERV expression demonstrated great variation and was significantly lower in pancreas compared to other tissues. More importantly, PERV RNA expression was found to be specifically enriched in pancreatic islets reaching values similar to those found in other tissues such as liver and kidney. Interestingly, this expression was not coupled with the detection of reverse transcriptase in islet cultures or indeed detection of PERV virus. Lung, spleen, and lymph node consistently showed the highest levels of PERV expression. Comparison of PERV in neonatal and adult pigs showed that copy number did not vary significantly from birth to adulthood. PERV expression on the other hand was significantly lower in neonatal pig islets compared to adult islets and did not increase over the period of culture. Our study confirms the low level of PERV expression in whole pancreas in a large population of both neonatal and adult pigs (n=80). The level of PERV expression was however higher in the endocrine tissue than in the exocrine cells. There was no correlation between PERV status in donor PBMCs and islet cells, and no evidence of active replication in in vitro regardless of PERV expression in islet cells. Moreover, neonatal pig islets were found to have significantly lower PERV expression compared to adult islets. Neonatal islets have been suggested as the best choice for xenotransplantation in terms of economic and procurement considerations; the PERV status reported here would also potentially support their use.


Concurrent insulinoma and impaired glucose tolerance suspected as owing to obesity.
An obese 68-year-old woman was admitted for examination of fasting hypoglycaemia. A prolonged 18 h fast reduced her plasma glucose without suppressing insulin secretion, while plasma β-hydroxybutyrate levels were suppressed. Despite the prolonged fast, the glucose response to glucagon was increased by 25 mg/dL (1.39 mM) glucose, which is compatible with insulinoma. A 75 g oral glucose tolerance test (75 g OGTT) showed impaired glucose tolerance. An abdominal CT scan revealed a mass lesion in the uncinate process of the pancreas, a finding consistent with the results of angiography and selective artery calcium injection test. The patient then underwent a pancreaticoduodenectomy; the pancreatic mass was histologically diagnosed as benign insulinoma. After surgery, a prolonged 24 h fast caused no hypoglycaemia and the glucose tolerance capacity in 75 g OGTT improved. Eight months after surgery, the patient's body weight had reduced by 10 kg. This is therefore a case of concurrent insulinoma and impaired glucose tolerance.


Male phenotypes in a female framework: Evidence for degeneration in sperm produced by male snails from asexual lineages.
How changes in selective regimes affect trait evolution is an important open biological question. We take advantage of naturally occurring and repeated transitions from sexual to asexual reproduction in a New Zealand freshwater snail species, Potamopyrgus antipodarum, to address how evolution in an asexual context-including the potential for relaxed selection on male-specific traits-influences sperm morphology. The occasional production of male offspring by the otherwise all-female asexual P. antipodarum lineages affords a unique and powerful opportunity to assess the fate of sperm traits in a context where males are exceedingly rare. These comparisons revealed that the sperm produced by 'asexual' males are markedly distinct from sexual counterparts. We also found that the asexual male sperm harboured markedly higher phenotypic variation and was much more likely to be morphologically abnormal. Together, these data suggest that transitions to asexual reproduction might be irreversible, at least in part because male function is likely to be compromised. These results are also consistent with a scenario where relaxed selection and/or mutation accumulation in the absence of sex translates into rapid trait degeneration.


Spectrophotometric measurements of human tissues for the detection of subjacent blood vessels in an endonasal endoscopic surgical approach.
Thin slices of human tissues are characterized concerning reflection and transmission in a wavelength range from 400 to 1700 nm. The results are primarily useful to find a wavelength for the detection of subjacent blood vessels during surgical procedures, especially neurological surgery. The measurements have been conducted using a customized measuring station, utilizing two halogen bulb lamps and two spectrometers. This paper focuses on creating a data base with the optical properties of artery, brain, bone, nasal mucosa, and nerve. The spectral distributions are compared among each other, similarities and differences are pointed out. Each tissue has got unique spectral characteristics, whereas typical absorption bands can be found in the overall tissues, especially hemoglobin and water absorption bands. The reflectivity maxima are typically located in the red or near-infrared. All the transmission maxima are located between 1075 nm and 1100 nm. The measurements have been conducted at the Institute of Anatomy at the University of Leipzig.


Reliability and validity of a physical activity social support assessment scale in adolescents--ASAFA Scale.
To analyze the reliability and validity of a scale used to measure social support for physical activity in adolescents - ASAFA Scale. This study included 2,755 adolescents (57.6% girls, 16.5 ± 1.2 years of age), from Joao Pessoa, Paraiba, Brazil. Initially, the scale was consisted of 12 items (6 for social support from parents and 6 from friends). The reliability of the scale was estimated by Cronbach's alpha coefficient (α), by the Composite Reliability (CR), and by the model with two factors and factorial invariance by Confirmatory Factor Analysis (CFA) adequacy. The CFA results confirmed that the social support scale contained two factors (factor 1: social support from parents; factor 2: social support from friends) with five items each (one item was excluded from each scale), all with high factor loadings (> 0.65) and acceptable adjustment indexes (RMR = 0.050; RMSEA = 0.063; 90%CI: 0.060 - 0.067); AGFI = 0.903; GFI = 0.940; CFI = 0.934, NNFI = 0.932). The internal consistency was satisfactory (parents: α ≥ 0.77 and CR ≥ 0.83; friends: α ≥ 0.87 and CR ≥ 0.91). The scale's factorial invariance was confirmed (p > 0.05; Δχ2 and ΔCFI ≤ 0.01) across all subgroups analyzed (gender, age, economic class). The construct validity was evidenced by the significant association (p < 0.05) between the adolescents physical activity level and the social support score of parents (rho = 0.29) and friends (rho = 0.39). The scale showed reliability, factorial invariance and satisfactory validity, so it can be used in studies with adolescents.


Sources of inputs to the anterior and posterior aspects of the paraventricular nucleus of the thalamus.
The paraventricular nucleus of the thalamus (PVT) is part of a group of midline and intralaminar thalamic nuclei implicated in arousal and attention. Recent research points to anatomical and functional differences between the anterior (aPVT) and posterior PVT (pPVT). The present study re-examines the main sources of brain inputs to the aPVT and pPVT in the rat following iontophoretic injections of the retrograde tracer cholera toxin B (CTb) in the PVT. The location and the number of retrogradely labeled neurons in different regions of the brain were examined to determine which brain areas are likely to exert a strong influence on the aPVT and pPVT. The largest number of labeled neurons was found in layer 6 of the prelimbic, infralimbic and posterior insular cortices following injections in the pPVT. In contrast, the largest number of labeled neurons following injections of CTb in the aPVT was found to be in the hippocampal subiculum and the prelimbic cortex. Other areas of the brain including the reticular nucleus of the thalamus, periaqueductal gray, parabrachial nucleus and dorsomedial nucleus of the hypothalamus were found to contain a more moderate number of neurons following injections of CTb in either the aPVT or pPVT. The results of the present tracing study clearly show that more neurons in the prefrontal cortex and subiculum project to the PVT than neurons from the hypothalamus and brainstem. These results highlight the potential importance of top-down modulation of PVT mechanisms and behavioral functions.


Concatenated Spatially-localized Random Forests for Hippocampus Labeling in Adult and Infant MR Brain Images.
Automatic labeling of the hippocampus in brain MR images is highly demanded, as it has played an important role in imaging-based brain studies. However, accurate labeling of the hippocampus is still challenging, partially due to the ambiguous intensity boundary between the hippocampus and surrounding anatomies. In this paper, we propose a concatenated set of spatially-localized random forests for multi-atlas-based hippocampus labeling of adult/infant brain MR images. The contribution in our work is two-fold. First, each forest classifier is trained to label just a specific sub-region of the hippocampus, thus enhancing the labeling accuracy. Second, a novel forest selection strategy is proposed, such that each voxel in the test image can automatically select a set of optimal forests, and then dynamically fuses their respective outputs for determining the final label. Furthermore, we enhance the spatially-localized random forests with the aid of the auto-context strategy. In this way, our proposed learning framework can gradually refine the tentative labeling result for better performance. Experiments show that, regarding the large datasets of both adult and infant brain MR images, our method owns satisfactory scalability by segmenting the hippocampus accurately and efficiently.


On the quantification of local power densities in a new vibration bioreactor.
We investigate the power densities which are obtainable locally in a vibration bioreactor. These reactor systems are of great relevance for research about oncological or antibacterial therapies. Our focus lies on the local liquid pressure caused by resonance vibration in the fluid contained by the reactor's petri dish. We use for the excitation one piezoelectric patch which offer advantages concerning controllability and reproducibility, when compared to ultrasound. The experimental work is extended by finite element analyses of bioreactor details. The peaks of the vibration response for water, sodium chloride (0.1N Standard solution), and McCoy's 5A culture medium are in good alignment. Several natural frequencies can be observed. Local power density can reach multiple times the magnitude used in ultrasound studies. Based on the observed local power densities, we are planning future work for the exposure of cell cultures to mechanical vibration.


A novel mesoporous biomaterial for treating dentin hypersensitivity.
An ideal material has yet to be discovered that can completely treat dentin hypersensitivity; however, calcium phosphate precipitation has exhibited potential value for the treatment of dentin hypersensitivity by the occlusion of dentinal tubules. We hypothesized that a novel mesoporous silica biomaterial (nano CaO@mesoporous silica, NCMS) containing nano-sized calcium oxide particles mixed with 30% phosphoric acid can efficiently occlude dentinal tubules and significantly reduce dentin permeability, even with the presence of pulpal pressure. This highly supersaturated Ca(2+)-and HPO(4)(2-)ion-containing NCMS paste was brushed onto dentin surfaces, and the ions diffused deeply into the dentinal tubules and formed a CaHPO(4).2H(2)O precipitation with a depth of 100 microm. The results of the dentin permeability tests showed that the novel mesoporous material exhibited a significant reduction in dentin permeability (p < 0.05), even under simulated pulpal pressure, as compared with our previously developed material, DP-bioglass, and a commercial desensitizing material, Seal & Protect.


Effect of postoperative analgesia on major postoperative complications: a systematic update of the evidence.
Few individual clinical trials have had sufficient subject numbers to definitively determine the effects of postoperative analgesia on major outcomes. We systematically searched the Medline and the Cochrane Library databases for the past decade and focused on meta-analyses and large, randomized, controlled trials. Eighteen meta-analyses, 10 systematic reviews, 8 additional randomized, controlled trials, and 2 observational database articles were identified for review or comment. Epidural analgesia with local anesthetics has the greatest theoretical potential to affect major outcomes and has been the most thoroughly investigated technique. The majority of evidence favors an ability of epidural analgesia to reduce postoperative cardiovascular and pulmonary complications only after major vascular surgery or in high-risk patients. This finding may become irrelevant because of rapid conversion of major surgery to minimally invasive techniques (e.g., endoluminal abdominal aortic repair) that carry less risk of complications. There is also consistent evidence that epidural analgesia with local anesthetics is associated with faster resolution of postoperative ileus after major abdominal surgery. Again, this finding may also become irrelevant with the adoption of laparoscopic techniques and multimodal fast-track programs for abdominal surgery. There is no current evidence that perineural analgesia, continuous wound catheters using local anesthetics, IV patient-controlled analgesia with opioids, or addition of multimodal systemic analgesics have any clinically significant beneficial effect on postoperative complications. Overall, there is insufficient evidence to confirm or deny the ability of postoperative analgesic techniques to affect major postoperative mortality or morbidity. This is primarily due to typically insufficient subject numbers to detect differences in currently low incidences of postoperative complications.


Confrontation naming does not add incremental diagnostic utility in MCI and Alzheimer's disease.
As the incidence of dementia increases, there is a growing need to determine the diagnostic utility of specific neuropsychological tests in the early diagnosis of Alzheimer's disease (AD). In this study, the relative utility of Boston Naming Test (BNT) in the diagnosis of AD was examined and compared to the diagnostic utility of other neuropsychological measures commonly used in the evaluation of AD. Individuals with AD (n = 306), Mild Cognitive Impairment (MCI; n = 67), and cognitively normal subjects (n = 409) with at least 2 annual evaluations were included. Logistic regression analysis suggested that initial BNT impairment is associated with increased risk of subsequent AD diagnosis. However, this risk is significantly less than that imparted by measures of delayed recall impairments. A multivariate Cox proportional hazards regression analysis suggested that BNT impairment imparted no additional risk for subsequent AD diagnosis after delayed recall impairments were included in the model. Although BNT impairment occurred in all severity groups, it was ubiquitous only in moderate to severe dementia. Collectively these results suggest that although BNT impairments become more common as AD progresses, they are neither necessary for the diagnosis of AD nor particularly useful in identifying early AD.


Advances in the diagnosis and treatment of tuberculous meningitis.
Early diagnosis and treatment of tuberculous meningitis (TBM) saves lives, but current laboratory diagnostic tests lack sensitivity and the best treatment regimens are uncertain. This article reviews the advances towards better TBM diagnosis and treatments made over the last 2 years. A modified Ziehl-Neelsen stain, interferon-gamma release assays and Mycobacterium tuberculosis antigen detection assays have all shown promise as new TBM diagnostic tests. HIV-associated TBM carries an especially grave prognosis and there are new data describing the optimal timing of antiretroviral treatment initiation and the clinical predictors of TBM immune reconstitution inflammatory syndrome. The pharmacokinetic and pharmacodynamic properties of different fluoroquinolones for TBM treatment have been compared, and there are intriguing new data to suggest higher doses of rifampicin given intravenously may improve the survival. Finally, there are preliminary data to suggest that the beneficial effect of adjunctive corticosteroids on TBM survival may be augmented by aspirin and predicted by a polymorphism in a gene responsible for eicosanoid synthesis. Much remains to be done to improve the outcome from TBM. There have been important advances in the treatment, which may influence treatment guidelines in the near future, but there remains an urgent need for better diagnostic tests.


Isoflurane and coronary heart disease.
Early studies indicated that isoflurane caused coronary steal and should therefore be avoided in patients with coronary heart disease. Subsequently, more detailed trials have disputed this and have shown that as long as coronary perfusion pressure is maintained, isoflurane does not cause coronary steal or myocardial ischaemia. There is now growing evidence, initially in animal work but more recently in human studies, that isoflurane has myocardial protective properties, limiting infarct size and improving functional recovery from myocardial ischaemia. The mechanism for this protection mimics ischaemic preconditioning and involves the opening of adenosine triphosphate-dependent potassium channels. The few studies comparing the myocardial protection offered by individual anaesthetic agents indicate that isoflurane represents the anaesthetic agent of choice for patients with coronary heart disease.


Older consumers' perceptions of health care information sources: the effect on search behavior.
Substantial evidence has been developed regarding the identity of health care information sources preferred by the elderly. However, this research has not empirically investigated why a given source might be more or less important to this segment. To address this gap, this research investigates OTC-health care information sources in terms of their credibility, expertise and associated risk. Differences in perceptions of these characteristics across the derived information source types are then examined across heavy and light users of OTC medications.


Standardized Mental Status Testing on the Sideline After Sport-Related Concussion.
OBJECTIVE: The effects of concussion on mental status are often difficult to assess on routine clinical examination. I investigated the efficacy of standardized mental status testing on the sport sideline to detect abnormalities that result from concussion and provide an objective measure of postinjury cognitive recovery. DESIGN AND SETTING: All subjects underwent a standardized preseason baseline mental status evaluation. Standardized testing of injured and uninjured control subjects was repeated on the sideline immediately after concussion and 48 hours after injury. SUBJECTS: Sixty-three high school and collegiate football players with concussion and 55 uninjured control subjects were studied. MEASUREMENTS: The Standardized Assessment of Concussion (SAC) was administered to evaluate neurocognitive functioning and neurologic status. RESULTS: Immediately after concussion, injured subjects performed significantly below preinjury baseline and below uninjured controls on the SAC. Measurable deficits in orientation, concentration, and memory were evident immediately after concussion. A decline in SAC score at time of injury was 95% sensitive and 76% specific in accurately classifying injured and uninjured subjects on the sideline. Injured subjects demonstrated significant improvements in SAC score 48 hours after injury. CONCLUSIONS: Standardized mental status testing can be a valuable tool to assist the sports medicine clinician in detecting the immediate effects of concussion on mental status, tracking resolution of immediate postconcussive mental status abnormalities, and making more informed decisions on return to play after injury.


Influence of ration composition on nutritive and digestive variables in captive giraffes (Giraffa camelopardalis) indicating the appropriateness of feeding practice.
The nutrition of captive giraffe (Giraffa camelopardalis), a browsing ruminant, is challenging because browse availability is limited in zoos and rations need to be composed of compensatory feeds. In this study, ration composition for giraffes in 12 German zoos was documented and linked to animal variables that indicate suitability of nutrition. Rations differed in proportion of ration items and chemical composition resulting in various grades of accordance with feeding recommendations. An estimated daily metabolisable energy (ME) intake (MEI; mean ± SD) of 0.61 MJ ME/kg0.75 body weight (BW; ±0.1) was sufficient to cover estimated energy requirements. Daily dry matter (DM) intake (DMI) was 61 g DM/kg0.75 BW (±10) and correlated negatively to dietary ME content (p = .009; r = -.596). Apparently, feed intake was regulated by energetic satiety and not by physical properties of forage. A negative correlation between produce proportion and DMI (p = .002; r = -.676) led to the assumption of a low ruminal pH in giraffes fed high proportions of produce. Increasing dietary forage proportions led to an increasing duration of feed intake (p = .045; r = .477) and decreasing occurrence of oral stereotypies (p = .047; r = -.474). The weighted average faecal particle size was larger than reported for free-ranging giraffes, but no relation to ration characteristics among the facilities existed. The abrasiveness of rations was not excessive, as contents of silicate in faeces were similar to values from the wild. Body condition was generally acceptable, but there was no evident relation to ration characteristics. The capacity to self-regulate DM and ME intakes with lucerne hay may work at higher forage proportions than often assumed for captive giraffes. Rations with less energetic density can result in a greater DMI, including maximisation of forage intake and reduction of oral stereotypies.


Rapid desensitization of alpha 1 beta 1 GABA A receptors expressed in Sf9 cells under optimized conditions.
alpha 1 and beta 1 subunits of human GABA A receptors were expressed in Sf9 cells using the Sf9-baculovirus system. Better expression was obtained by manipulating the system. Cell growth phase at the time of infection determined the practical range of virus titre, the period postinfection during which cells were useful for signal detection and the maximal current obtained. Cells in the early exponential phase were relatively insensitive to multiplicity of infection (MOI) whereas cells in the mid- to late-exponential phase were highly dependent on MOI and they responded with the largest Cl- current generated by GABA. Channels activated by GABA were chloride-selective. Half the maximum peak whole-cell current was obtained with 11 microM GABA. The time course of Cl- currents activated by saturating GABA concentrations in cells infected with alpha 1 beta 1-recombinant viruses was examined employing a rapid perfusion system which allowed whole-cell solution exchange in less than 1 msec. The current decay could be fitted by 3 to 4 exponentials for the first 8 sec. The initial fast current decrease had a time constant of about 23 msec. No voltage dependence of time constants was detected but the whole-cell IV relation showed outward rectification. Currents were depressed by bicuculline, penicillin and picrotoxin and potentiated by pentobarbitone.


New Continuous Miniature Crystal Element (cMiCE) Detector Geometries.
Continuous miniature crystal element (cMiCE) detectors are a potentially lower cost alternative to high resolution discrete crystal designs. We report on the intrinsic spatial resolution performance for two cMiCE PET detector designs with depth of interaction (DOI) positioning capability. The first detector utilizes a 50 mm by 50 mm by 8 mm LYSO crystal coupled to a 64 channel, multi-anode PMT. It provides 4 layers of DOI information. The crystal has beveled edges along two of its sides to improve the detector packing when placed in a ring geometry. The second detector utilizes a 50 mm by 50 mm by 15 mm, rectangular LYSO crystal coupled to a 64 channel, multi-anode PMT. It provides up to 15 layers of DOI information. The average intrinsic X, Y spatial resolution for the 8 mm thick, truncated crystal detector was 1.33 +/- 0.31 mm FWHM (45.6 mm by 46.6 mm useful imaging area). The average DOI resolution was 3.5 +/- 0.22 mm. The average intrinsic X, Y spatial resolution for the 15 mm thick crystal detector was 1.74 +/- 0.35 mm FWHM (44.6 mm by 44.6 mm useful imaging area). In addition, the average DOI spatial resolution for 56 test points spanning a 26.4 mm by 12.2 mm region of the crystal was 4.80 +/- 0.36 mm. We believe the 8 mm thick truncated crystal design is suitable for mouse imaging while the 15 mm thick crystal design is more suited for human organ specific imaging systems (e.g., breast and brain).


Successful Introduction of Full-Endoscopic Lumbar Interlaminar Discectomy in Sweden.
The introduction of full-endoscopic lumbar discectomy (FELD) procedures has made it possible to challenge microscopic discectomy as the gold standard method to treat lumbar disc herniations. The aim of the present study is to investigate the introductory-phase postoperative clinical improvement for FELD patients regarding leg pain, patient-reported outcome measurements (PROMs), complications, reoperations, and learning curve analysis. All patients who underwent FELD at Sahlgrenska University Hospital, Sweden, were prospectively included during 2013- 2017. A total of 92 patients were enrolled and followed up for 1 year. The characteristics of the study population, degree of leg pain, complications, learning curve, and PROMs were retrieved from patient records and the National Quality Register for Spine Surgery (Swespine). The postoperative results demonstrated major improvements; leg pain measured by a numerical rating scale (0-10) decreased from 7.4 ± 2.25 to 2.76 ± 2.70, with a mean improvement of -4.54, (-3.62-5.46) 95% confidence interval (CI). The Oswestry Disability Index decreased by 30.48 (-36.27-23.73) with a 95% CI, and the EuroQol-5D increased by 0.39 (0.21-0.57) 95% CI. An assessment of the final surgical result showed that 91.6% ranked their general situation as better or much better. Specifically, regarding postoperative leg pain, 87% regarded their leg pain as completely gone, much better, or somewhat better, while 13% regarded their leg pain as unchanged or worse. A learning curve analysis showed that for every 10th FELD procedure performed; the duration of surgery decreased by 2 minutes. In our study, the introduction of FELD as a safe, quick procedure for the treatment of lumbar disc herniations can yield significant gains in patient-reported outcome measurements and pain reduction. The rate of recurrence and complications is comparable to that of standard surgery.


Theoretical and experimental analyses of GAWBS phase noise in various optical fibers for digital coherent transmission.
We describe the fiber structural dependence of guided acoustic-wave Brillouin scattering (GAWBS) phase noise in a digital coherent optical fiber transmission. We present theoretical and experimental analyses of GAWBS phase noise spectra in three types of optical fibers and show that the GAWBS resonant modes are distributed over a wider bandwidth as the effective core area of the fiber becomes smaller. We also use a vector signal analysis to show phase fluctuations caused by GAWBS. On the basis of these analyses, we show that the GAWBS phase noise fluctuation has a Gaussian distribution, which is used to evaluate its influence on the BER characteristics in a coherent QAM transmission. As a result, we found that the error-free transmission distance in SSMF is limited to 4600, 1200, and 340 km with 64, 256, and 1024 QAM, respectively, assuming a hard-decision FEC with a 7% overhead. These results provide useful insights into the influence of GAWBS on digital coherent transmission.


Hsp72 (HSPA1A) Prevents Human Islet Amyloid Polypeptide Aggregation and Toxicity: A New Approach for Type 2 Diabetes Treatment.
Type 2 diabetes is a growing public health concern and accounts for approximately 90% of all the cases of diabetes. Besides insulin resistance, type 2 diabetes is characterized by a deficit in β-cell mass as a result of misfolded human islet amyloid polypeptide (h-IAPP) which forms toxic aggregates that destroy pancreatic β-cells. Heat shock proteins (HSP) play an important role in combating the unwanted self-association of unfolded proteins. We hypothesized that Hsp72 (HSPA1A) prevents h-IAPP aggregation and toxicity. In this study, we demonstrated that thermal stress significantly up-regulates the intracellular expression of Hsp72, and prevents h-IAPP toxicity against pancreatic β-cells. Moreover, Hsp72 (HSPA1A) overexpression in pancreatic β-cells ameliorates h-IAPP toxicity. To test the hypothesis that Hsp72 (HSPA1A) prevents aggregation and fibril formation, we established a novel C. elegans model that expresses the highly amyloidogenic human pro-IAPP (h-proIAPP) that is implicated in amyloid formation and β-cell toxicity. We demonstrated that h-proIAPP expression in body-wall muscles, pharynx and neurons adversely affects C. elegans development. In addition, we demonstrated that h-proIAPP forms insoluble aggregates and that the co-expression of h-Hsp72 in our h-proIAPP C. elegans model, increases h-proIAPP solubility. Furthermore, treatment of transgenic h-proIAPP C. elegans with ADAPT-232, known to induce the expression and release of Hsp72 (HSPA1A), significantly improved the growth retardation phenotype of transgenic worms. Taken together, this study identifies Hsp72 (HSPA1A) as a potential treatment to prevent β-cell mass decline in type 2 diabetic patients and establishes for the first time a novel in vivo model that can be used to select compounds that attenuate h-proIAPP aggregation and toxicity.


Transparent Dual-Frequency CMUT Arrays for Photoacoustic Imaging.
The opaque ultrasound transducers used in conventional photoacoustic imaging systems necessitate oblique light delivery, which gives rise to some disadvantages such as inefficient target illumination and bulky system size. This work proposes a transparent capacitive micromachined ultrasound transducer (CMUT) linear array with dual-band operation for through-illumination photoacoustic imaging. Fabricated using an adhesive wafer bonding method, the array consists of optically transparent conductors [indium tin oxide (ITO)] as both top and bottom electrodes, a transparent polymer [bisbenzocyclobutene (BCB)] as the sidewall and adhesive material, and largely transparent silicon nitride as the membrane. The fabricated device had a maximum optical transparency of 76.8% in the visible range. Furthermore, to simultaneously maintain higher spatial resolution and deeper imaging depth, this dual-frequency array consists of low- and high-frequency channels with 4.2- and 9.3-MHz center frequencies, respectively, which are configured in an interlaced architecture to minimize the grating lobes in the receive point spread function (PSF). With a wider bandwidth compared to the single-frequency case, the fabricated transparent dual-frequency CMUT array was used in through-illumination photoacoustic imaging of wire targets demonstrating an improved spatial resolution and imaging depth.


Improving Radiographic Fracture Recognition Performance and Efficiency Using Artificial Intelligence.
Background Missed fractures are a common cause of diagnostic discrepancy between initial radiographic interpretation and the final read by board-certified radiologists. Purpose To assess the effect of assistance by artificial intelligence (AI) on diagnostic performances of physicians for fractures on radiographs. Materials and Methods This retrospective diagnostic study used the multi-reader, multi-case methodology based on an external multicenter data set of 480 examinations with at least 60 examinations per body region (foot and ankle, knee and leg, hip and pelvis, hand and wrist, elbow and arm, shoulder and clavicle, rib cage, and thoracolumbar spine) between July 2020 and January 2021. Fracture prevalence was set at 50%. The ground truth was determined by two musculoskeletal radiologists, with discrepancies solved by a third. Twenty-four readers (radiologists, orthopedists, emergency physicians, physician assistants, rheumatologists, family physicians) were presented the whole validation data set (n = 480), with and without AI assistance, with a 1-month minimum washout period. The primary analysis had to demonstrate superiority of sensitivity per patient and the noninferiority of specificity per patient at -3% margin with AI aid. Stand-alone AI performance was also assessed using receiver operating characteristic curves. Results A total of 480 patients were included (mean age, 59 years ± 16 [standard deviation]; 327 women). The sensitivity per patient was 10.4% higher (95% CI: 6.9, 13.9; P < .001 for superiority) with AI aid (4331 of 5760 readings, 75.2%) than without AI (3732 of 5760 readings, 64.8%). The specificity per patient with AI aid (5504 of 5760 readings, 95.6%) was noninferior to that without AI aid (5217 of 5760 readings, 90.6%), with a difference of +5.0% (95% CI: +2.0, +8.0; P = .001 for noninferiority). AI shortened the average reading time by 6.3 seconds per examination (95% CI: -12.5, -0.1; P = .046). The sensitivity by patient gain was significant in all regions (+8.0% to +16.2%; P < .05) but shoulder and clavicle and spine (+4.2% and +2.6%; P = .12 and .52). Conclusion AI assistance improved the sensitivity and may even improve the specificity of fracture detection by radiologists and nonradiologists, without lengthening reading time. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Link and Pedoia in this issue.


Illuminating G-Protein-Coupling Selectivity of GPCRs.
Heterotrimetic G proteins consist of four subfamilies (Gs, Gi/o, Gq/11, and G12/13) that mediate signaling via G-protein-coupled receptors (GPCRs), principally by receptors binding Gα C termini. G-protein-coupling profiles govern GPCR-induced cellular responses, yet receptor sequence selectivity determinants remain elusive. Here, we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique Gα subunit C termini. For each receptor, we probed chimeric Gα subunit activation via a transforming growth factor-α (TGF-α) shedding response in HEK293 cells lacking endogenous Gq/11 and G12/13 proteins, and complemented G-protein-coupling profiles through a NanoBiT-G-protein dissociation assay. Interrogation of the dataset identified sequence-based coupling specificity features, inside and outside the transmembrane domain, which we used to develop a coupling predictor that outperforms previous methods. We used the predictor to engineer designer GPCRs selectively coupled to G12. This dataset of fine-tuned signaling mechanisms for diverse GPCRs is a valuable resource for research in GPCR signaling.


Motion-robust, multi-slice, real-time MR thermometry for MR-guided thermal therapy in abdominal organs.
To develop an effective and practical reconstruction pipeline to achieve motion-robust, multi-slice, real-time MR thermometry for monitoring thermal therapy in abdominal organs. The application includes a fast spiral magnetic resonance imaging (MRI) pulse sequence and a real-time reconstruction pipeline based on multi-baseline proton resonance frequency shift (PRFS) method with visualization of temperature imaging. The pipeline supports multi-slice acquisition with minimal reconstruction lag. Simulations with a virtual motion phantom were performed to investigate the influence of the number of baselines and respiratory rate on the accuracy of temperature measurement. Phantom experiments with ultrasound heating were performed using a custom-made motion phantom to evaluate the performance of the pipeline. Lastly, experiments in healthy volunteers (N = 2) without heating were performed to evaluate the accuracy and stability of MR thermometry in abdominal organs (liver and kidney). The multi-baseline approach with greater than 25 baselines resulted in minimal temperature errors in the simulation. Phantom experiments demonstrated a 713 ms update time for 3-slice acquisitions. Temperature maps with 30 baselines showed clear temperature distributions caused by ultrasound heating in the respiratory phantom. Finally, the pipeline was evaluated with physiologic motions in healthy volunteers without heating, which demonstrated the accuracy (root mean square error [RMSE]) of 1.23 ± 0.18 °C (liver) and 1.21 ± 0.17 °C (kidney) and precision of 1.13 ± 0.11 °C (liver) and 1.16 ± 0.15 °C (kidney) using 32 baselines. The proposed real-time acquisition and reconstruction pipeline allows motion-robust, multi-slice, real-time temperature monitoring within the abdomen during free breathing.


Enhancing in vivo tumor boundary delineation with structured illumination fluorescence molecular imaging and spatial gradient mapping.
Fluorescence imaging, in combination with tumor-avid near-infrared (NIR) fluorescent molecular probes, provides high specificity and sensitivity for cancer detection in preclinical animal models, and more recently, assistance during oncologic surgery. However, conventional camera-based fluorescence imaging techniques are heavily surface-weighted such that surface reflection from skin or other nontumor tissue and nonspecific fluorescence signals dominate, obscuring true cancer-specific signals and blurring tumor boundaries. To address this challenge, we applied structured illumination fluorescence molecular imaging (SIFMI) in live animals for automated subtraction of nonspecific surface signals to better delineate accumulation of an NIR fluorescent probe targeting α4β1 integrin in mice bearing subcutaneous plasma cell xenografts. SIFMI demonstrated a fivefold improvement in tumor-to-background contrast when compared with other full-field fluorescence imaging methods and required significantly reduced scanning time compared with diffuse optical spectroscopy imaging. Furthermore, the spatial gradient mapping enhanced highlighting of tumor boundaries. Through the relatively simple hardware and software modifications described, SIFMI can be integrated with clinical fluorescence imaging systems, enhancing intraoperative tumor boundary delineation from the uninvolved tissue.


Modulation of the reactivity of nitrogen mustards by metal complexation: approaches to modify their therapeutic properties.
The alkylating agents bearing the -N(CH2CH2Cl)2 moiety, commonly known as 'the nitrogen mustards,' are among the first chemotherapeutic agents against cancer. They form covalent alkyl linkages due to reaction with nucleophilic entities viz. N7 of guanine in DNA. The reactivity of nitrogen mustards may be controlled in various ways, which include metabolic activation, reductive or hypoxic activation and metal complexation. This review discusses how the metal complexation of nitrogen mustards affects their reactivity and mechanistic pathways. The discussion encompasses those transition metal complexes for which the structure has been well characterized and cytotoxicity studies have been performed. This review discusses how the binding of the metal centre along with its oxidation state helps to control the reactivity of the nitrogen mustards. The discussion emphasizes the effect of the reduction potential of the coordinated metal center on the reactivity of the respective mustard under specific conditions, the dependence of efficiency and specificity on the stability of the reduced species and the importance of steric hindrance around the metal center. The insight into the mechanism of action is expected to provide a better understanding to overcome the existing lacunae and design better molecules of this class which have excellent potential, given the ever growing need for therapeutics against cancer.


Is observation dead in follicular lymphoma? No, but the apoptosis pathway has been activated.
Follicular lymphoma (FL), the most common indolent type of non-Hodgkin's lymphoma, presents with a highly variable clinical course and affects the overall survival (OS) of patients. Although observation has been adopted widely by clinicians in the management of patients with FL, the benefits of early treatment must be reviewed in light of the significant progress made in the treatment of symptomatic or higher-tumor-burden FL. When treatment is indicated, a variety of combination chemotherapeutic regimens have proven efficacy and have shown improvements in both progression-free and event-free survival, and the addition of rituximab to these regimens has shown a statistically significant improvement in OS. Additionally, single-agent rituximab has been added to the possible therapeutic options for patients with low-tumor-burden FL. Although a paucity of clinical data exists on the upfront treatment of the low-tumor-burden population, the question of whether early treatment, especially with the newer rituximab-containing chemotherapy regimens, would improve OS is thought-provoking. Furthermore, novel targeted therapies with tolerable side effect profiles are rapidly advancing in the treatment of non-Hodgkin's lymphoma. The future for patients with low-tumor-burden FL is brighter than ever before.


Immune-inflammatory markers in patients with seasonal affective disorder: effects of light therapy.
There is increasing evidence that an activation of the immune-inflammatory system is involved in the pathophysiology of depressive disorders. The purposes of this study were to (1) compare immune-inflammatory markers in patients with seasonal affective disorder (SAD) with those in matched normal controls; and (2) examine the effects of light therapy on the immune-inflammatory markers in patients with SAD. Plasma concentrations of interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R) and soluble IL-2 receptor (sIL-2R) were measured in 15 patients with SAD and 15 age- and sex-matched normal controls. Of the 15 patients, 14 had repeated blood sampling for these variables following 2 weeks of light therapy. We found that patients with SAD had significantly increased IL-6 levels compared to normal controls (P<0.0005). There was a trend toward increased sIL-2R in patients with SAD (P=0.09). There was no significant difference in sIL-6R level between the two diagnostic groups (P=0.18), but the product term (IL-6xsIL-6R) was significantly higher in patients with SAD than that in normal control controls (P<0.0003). Furthermore, all 14 patients who completed the study improved with 2 weeks of light therapy and nine of them (64%) had 50% reduction in score of the Hamilton Depression Rating Scale-SAD version post-treatment compared to baseline. However, the initially increased immune markers in SAD patients were not significantly altered by the therapeutic light therapy. This study was limited to a small sample size and other immune inflammatory markers should be measured for further evidence of immune activation in seasonal depression. Our results of increased IL-6, IL-6xsIL-6R, and sIL-2R in patients with SAD suggest an activation of the immune-inflammatory system in winter depression, which is not altered by 2 weeks of successful light therapy.


Opposing Regulation of Cancer Properties via KRT19-Mediated Differential Modulation of Wnt/β-Catenin/Notch Signaling in Breast and Colon Cancers.
Although Keratin 19 (KRT19) has been reported as a tumor cell marker and found to interact with other proteins that modulate cancer properties, its role in cancer prognosis remains to be fully elucidated. We found that KRT19 expression was increased in both colon and breast cancer, but that knockdown of KRT19 showed opposing effects on cancer properties. In colon cancer, KRT19 knockdown resulted in suppression of cancer via downregulation of Wnt/Notch signaling without altering NUMB transcription. In breast cancer, KRT19 knockdown led to an increase in cancer properties because of attenuated Wnt and enhanced Notch signaling. In colon cancer, KRT19 interacted with β-catenin but not with RAC1, allowing the LEF/TCF transcription factor to bind primarily to the LEF1 and TCF7 promoter regions, whereas in breast cancer, KRT19 interacted with the β-catenin/RAC1 complex and led to apparent upregulation of NUMB expression and NUMB-mediated suppression of Notch signaling. These results reveal a novel differential role of KRT19 in carcinogenesis, due to differential modulation of Wnt/β-catenin/Notch signaling crosstalk through various interactions of KRT19 with only β-catenin or with the β-catenin/RAC1 complex, which might have implications for clinical cancer research.


Old World monkeys are more similar to humans than New World monkeys when playing a coordination game.
There is much debate about how humans' decision-making compares with that of other primates. One way to explore this is to compare species' performance using identical methodologies in games with strategical interactions. We presented a computerized Assurance Game, which was either functionally simultaneous or sequential, to investigate how humans, rhesus monkeys and capuchin monkeys used information in decision-making. All species coordinated via sequential play on the payoff-dominant Nash equilibrium, indicating that information about the partner's choice improved decisions. Furthermore, some humans and rhesus monkeys found the payoff-dominant Nash equilibrium in the simultaneous game, even when it was the first condition presented. Thus, Old World primates solved the task without any external cues to their partner's choice. Finally, when not explicitly prohibited, humans spontaneously used language to coordinate on the payoff-dominant Nash equilibrium, indicating an alternative mechanism for converting a simultaneous move game into a sequential move game. This phylogenetic distribution implies that no single mechanism drives coordination decisions across the primates, while humans' ability to spontaneously use language to change the structure of the game emphasizes that multiple mechanisms may be used even within the same species. These results provide insight into the evolution of decision-making strategies across the primates.


[Comparison between endothelin binding sites and sarafotoxin S6B binding sites in rat tissues: studies by quantitative in vitro receptor autoradiography].
Sarafotoxin S6B(SRT), a peptide in snake venom, has a high degree of sequence homology with endothelin (ET) and both are potent vasoconstrictors. In order to determine whether SRT acts via the ET receptor, we performed autoradiographic binding studies on rat tissues using the radioligands, 125I-ET-1 and 125I-SRT and computerized in vitro autoradiography. In the heart, a high density of ET binding was found in the atria, and moderate density was found in the ventricles. A high density of ET-1 was found in the heart. In the kidney, ET-1 binding occurred in association with glomeruli, outer cortex, and inner stripe and inner medulla. In the adrenal, a high density of ET-1 binding occurred in the medulla as well as the zona glomerulosa. The binding affinity constant (KA) for ET-1 binding in these sites ranged from 1-10 x 10(9) M-1. Although SRT was 5-100 fold weaker than ET-1 in displacing 125I-ET-1 from these sites, 1 microM unlabelled SRT completely abolished 125I-ET-1 binding in all sites. Other venom peptides or unrelated peptides did not affect 125I-ET-1 binding. Moreover, the pattern of 125I-SRT binding in rat tissues by in vitro autoradiography was identical with that of 125I-ET-1 binding, and both unlabelled SRT and unlabelled ET-1 fully competed with 125I-SRT for binding. These results provide evidence that SRT binds to the ET binding sites in a range of rat tissues.


Fatty acid composition of some mycolic acid-containing coryneform bacteria.
The fatty acid profiles of 74 strains of mycolic acid-containing coryneform bacteria were examined by gas-liquid chromatography. All of the strains contained major amounts of straight-chain and monounsaturated fatty acids although some also possessed substantial amounts of 10-methyloctadecanoic acid. Iso- and anteiso-branched acids were not present. Five distinct fatty acid patterns were evident: (i) Corynebacterium diphtheriae, C. pseudotuberculosis and 'C. ulcerans' strains contained major amounts of hexadecanoic and hexadecenoic acids; (ii) C. glutamicum, C. xerosis and related saprophytic and animal-associated strains, predominantly hexadecanoic and octadecenoic acids; (iii) C. bovis, major amounts of octadecenoic and 10-methyloctadecanoic acids; (iv) 'C. mycetoides', significant amounts of heptadecanoic acid as well as hexadecanoic and octadecenoic acids; and (v) strains related to Rhodococcus possessed significant quantities of 10-methyloctadecanoic acid in addition to straight-chain and monounsaturated acids.


[2Fe-2S] proteins in Chlorosomes: redox properties of CsmI, CsmJ, and CsmX of the Chlorosome envelope of Chlorobaculum tepidum.
The chlorosome envelope of Chlorobaculum tepidum contains 10 polypeptides, three of which, CsmI, CsmJ, and CsmX, have an adrenodoxin-like domain harboring a single [2Fe-2S] cluster. Mutants that produced chlorosomes containing two, one, or none of these Fe-S proteins were constructed [Li, H., et al. (2013) Biochemistry 52, preceding paper in this issue ( DOI: 10.1021/bi301454g )]. The electron paramagnetic resonance (EPR) spectra, g values, and line widths of the Fe-S clusters in individual CsmI, CsmJ, and CsmX proteins were obtained from studies with isolated chlorosomes. The Fe-S clusters in these proteins were characterized by EPR and could be differentiated on the basis of their g values and line widths. The EPR spectrum of wild-type chlorosomes could be simulated by a 1:1 admixture of the CsmI and CsmJ spectra. No contribution of CsmX to the EPR spectrum of chlorosomes was observed because of its low abundance. In chlorosomes that contained only CsmI or CsmJ, the midpoint potential of the [2Fe-2S] clusters was -205 or 8 mV, respectively; the midpoint potential of the [2Fe-2S] cluster in CsmX was estimated to be more oxidizing than -180 mV. In wild-type chlorosomes, the midpoint potentials of the [2Fe-2S] clusters were -348 mV for CsmI and 92 mV for CsmJ. The lower potential for CsmI in the presence of CsmJ, and the higher potential for CsmJ in the presence of CsmI, were attributed to interactions that occur when these proteins form complexes in the chlorosome envelope. The redox properties of CsmI and CsmJ are consistent with their proposed participation in the transfer of electrons to and from quenchers of energy transfer in chlorosomes.


Parallel genetic and proteomic screens identify Msps as a CLASP-Abl pathway interactor in Drosophila.
Regulation of cytoskeletal structure and dynamics is essential for multiple aspects of cellular behavior, yet there is much to learn about the molecular machinery underlying the coordination between the cytoskeleton and its effector systems. One group of proteins that regulate microtubule behavior and its interaction with other cellular components, such as actin-regulatory proteins and transport machinery, is the plus-end tracking proteins (MT+TIPs). In particular, evidence suggests that the MT+TIP, CLASP, may play a pivotal role in the coordination of microtubules with other cellular structures in multiple contexts, although the molecular mechanism by which it functions is still largely unknown. To gain deeper insight into the functional partners of CLASP, we conducted parallel genetic and proteome-wide screens for CLASP interactors in Drosophila melanogaster. We identified 36 genetic modifiers and 179 candidate physical interactors, including 13 that were identified in both data sets. Grouping interactors according to functional classifications revealed several categories, including cytoskeletal components, signaling proteins, and translation/RNA regulators. We focused our initial investigation on the MT+TIP Minispindles (Msps), identified among the cytoskeletal effectors in both genetic and proteomic screens. Here, we report that Msps is a strong modifier of CLASP and Abl in the retina. Moreover, we show that Msps functions during axon guidance and antagonizes both CLASP and Abl activity. Our data suggest a model in which CLASP and Msps converge in an antagonistic balance in the Abl signaling pathway.


Botulism among Alaska natives in the Bristol Bay area of southwest Alaska: a survey of knowledge, attitudes, and practices related to fermented foods known to cause botulism.
Botulism cases due to traditional Alaska Native fermented foods occur periodically in Southwest Alaska. In this population, we conducted a survey on knowledge, attitudes, and practices related to botulism and fermented foods. We interviewed 140 adults randomly chosen from nine villages. Data collected included fermented food consumption frequency; knowledge about the cause and symptoms of botulism; and fermented food preparation methods. Most respondents (81%) had eaten Alaska Native fermented foods at least once. Over 70% identified botulism as a foodborne illness, and over 87% believed eating certain Native fermented foods could cause botulism. One-third of fermented food preparers used plastic containers for fermentation. To prevent botulism, 45% vwould consider boiling fermented foods, and 65% would not eat foods fermented in plastic or glass containers. Despite high awareness of botulism in this population, one-third of fermented food preparers use plastic containers, a practice which may increase the risk of botulism. Misconceptions and acceptable prevention messages about botulism, such as using traditional nonplastic fermentation methods, were identified and included in an educational video.


Meta-analysis: dietary fat intake, serum estrogen levels, and the risk of breast cancer.
There is compelling evidence that estrogens influence breast cancer risk. Since the mid-1980s, dietary fat intervention studies have been conducted to investigate the effect of fat intake on endogenous estrogen levels. To further our understanding of the possible relationship between dietary fat and breast cancer, we conducted a meta-analysis of dietary fat intervention studies that investigated serum estradiol levels, and we reviewed the nature of the evidence provided by prospective analytic studies of fat consumption and breast cancer risk. A computerized search of the English language literature on estrogen/estradiol and dietary fat intervention studies published from January 1966 through June 1998 was conducted using the MEDLINE database. Pooled estimates were derived from the change in estradiol levels associated with fat reduction from 13 studies. Analyses were conducted separately for premenopausal and postmenopausal women and in both groups combined. Statistically significant reductions in serum estradiol levels of -7.4% (95% confidence interval [CI] = -11.7% to -2.9%) among premenopausal women and -23.0% (95% CI = -27.7% to -18.1%) among postmenopausal women were observed, with an overall -13.4% (95% CI = -16.6% to -10.1%) reduction observed. The greatest reductions occurred in two studies in which dietary fat was reduced to 10%-12% of calories compared with 18%-25% of calories in the other studies. A statistically significant reduction in estradiol levels of -6.6% (95% CI = -10.3% to -2.7%) remained after exclusion of these two studies. Review of prospective analytic epidemiologic studies that allowed for dietary measurement error suggests that the possibility that reducing fat consumption below 20% of calories will reduce breast cancer risk cannot be excluded. Dietary fat reduction can result in a lowering of serum estradiol levels and such dietary modification may still offer an approach to breast cancer prevention.


[Pre-radiation care in proton irradiation of tumors of the cavernous sinus].
The authors described methods of the individual precision anatomodosimetric planning of proton-beam irradiation of tumors of the cavernous sinus. The results of computerized tomography in 2 planes (axial and frontal) were used for planning. Manual tumor reconstruction with subsequent dose planning was done on direct and lateral telecraniograms. The procedure was tested in 25 patients. Complications and noticeable radiation reactions in adjacent tissues were undetectable during 3.5 yrs.


[DNA-binding proteins in human serum].
Fractions of acid and base blood serum proteins, separated by ion exchange chromatography on QAE-Sephadex (but not the proteins of the whole blood serum, which had the same charge), reacted with DNA preparations. Separate fractions of blood serum proteins were able to react with DNA after electrophoretic separation. Binding of blood serum proteins with DNA did not depend on ion strength within the range of NaCl concentration from 0.1 M to 0.5 M; it was also stable at pH 5.5 = 8.0. Interaction between acid DNA-binding proteins and native DNA was inhibited by denatured DNA, polyguanilic and polyinosinic acids and by other polyanions: dextran sulfate, polyvinyl sulfate, polyanetol sulphonate, polystyrol sulphonate and heparin. Acid DNA-binding proteins showed only a slight affinity to polyadenilic, polyuridilic and polycytidilic acids. The acid and base DNA-binding proteins appear to be contained in blood serum in the form of a loosely bound complex.


Spontaneously occurring agglutinins in primate sera. II. Their classification and implications for the mechanism of antibody formation.
Spontaneously occurring agglutinins in animal sera are shown to fall into several categories, namely, 1. cold-reactive agglutinins; these often are nonspecific and act as autoagglutinins, 2. agglutinins reactive at room as well as refrigerator temperatures; these, like cold agglutinins, are usually IgM immunoglobulins which may be species-specific in their activity, or type-specific, notably, like anti-A and anti-B and 3. agglutinins reactive at body temperature, usually IgG immunoglobulins, and most often due to maternofetal incompatibility and transplacental immunization of the mother by fetal red cells. The naturally occurring cold autoantibodies are physiologic in nature and appear to be the raw materials for antibody production. This is postulated to be adaptive in nature by enzyme action, through in part genetically determined, as evidenced by the so-called constant polypeptide sections of the immunoglobulin molecules.


Functional outcome after treatment of lower-extremity nonunions.
The results for nonunion surgery usually have been judged in terms of bony union, time to union, infection rate, range of motion for the adjacent joints, and muscle strength. The goal of this study was to assess the improvement of patient-oriented physical and mental functional outcomes. The functional status of 23 patients with nonunion of the lower extremity was assessed using the Short-Form Health Survey (SF-36) questionnaire. The SF-36 subscores were compared with preoperative values and with the average values for the U.S. population. Of the 23 patients, 21 healed. The functional status for nonunions of the lower extremity was greatly improved 1 year after operative intervention in this study. Nevertheless, the results show that it did not reach the level of the average U.S. population. The results of this study can be used to guide patients' expectations regarding the functional outcome of treatment for a nonunion of the lower extremity.


Cardiopulmonary Exercise Test in the Detection of Unexplained Post-COVID-19 Dyspnea.
There is emerging evidence of prolonged recovery in survivors of coronavirus disease 2019 (COVID-19), even in those with mild COVID-19. In this paper, we report a case of a 39-year-old male with excessive body weight and a history of borderline values of arterial hypertension without therapy, who was mainly complaining of progressive dyspnea after being diagnosed with mild COVID-19. According to the recent guidelines on the holistic assessment and management of patients who had COVID-19, all preferred diagnostic procedures, including multidetector computed tomography (CT), CT pulmonary angiogram, and echocardiography, should be conducted. However, in our patient, no underlying cardiopulmonary disorder has been established. Therefore, considering all additional symptoms our patient had beyond dyspnea, our initial differential diagnosis included anxiety-related dysfunctional breathing. However, psychiatric evaluation revealed that our patient had only a mild anxiety level, which was unlikely to provoke somatic complaints. We decided to perform further investigations considering that cardiopulmonary exercise test (CPET) represents a reliable diagnostic tool for patients with unexplained dyspnea. Finally, the CPET elucidated the diastolic dysfunction of the left ventricle, which was the most probable cause of progressive dyspnea in our patient. We suggested that, based on uncontrolled cardiovascular risk factors our patient had, COVID-19 triggered a subclinical form of heart failure (HF) with preserved ejection fraction (HFpEF) to become clinically manifest. Recently, the new onset, exacerbation, or transition from subclinical to clinical HFpEF has been associated with COVID-19. Therefore, in addition to the present literature, our case should warn physicians on HFpEF among survivors of COVID-19.


Re-examination of the APETALA2/Ethylene-Responsive Factor Gene Family in Barley (Hordeum vulgare L.) Indicates a Role in the Regulation of Starch Synthesis.
The APETALA2/Ethylene-Responsive factor (AP2/ERF) gene family is a large plant-specific transcription factor family, which plays important roles in regulating plant growth and development. A role in starch synthesis is among the multiple functions of this family of transcription factors. Barley (Hordeum vulgare L.) is one of the most important cereals for starch production. However, there are limited data on the contribution of AP2 transcription factors in barley. In this study, we used the recently published barley genome database (Morex) to identify 185 genes of the HvAP2/ERF family. Compared with previous work, we identified 64 new genes in the HvAP2/ERF gene family and corrected some previously misannotated and duplicated genes. After phylogenetic analysis, HvAP2/ERF genes were classified into four subfamilies and 18 subgroups. Expression profiling showed different patterns of spatial and temporal expression for HvAP2/ERF genes. Most of the 12 HvAP2/ERF genes analyzed using quantitative reverse transcription-polymerase chain reaction had similar expression patterns when compared with those of starch synthase genes in barley, except for HvAP2-18 and HvERF-73. HvAP2-18 is homologous to OsRSR1, which negatively regulates the synthesis of rice starch. Luciferase reporter gene, and yeast one-hybrid assays showed that HvAP2-18 bound the promoter of AGP-S and SBE1 in vitro. Thus, HvAP2-18 might be an interesting candidate gene to further explore the mechanisms involved in the regulation of starch synthesis in barley.


Progressive valgus angulation of the ankle secondary to loss of fibular congruity treated with medial tibial hemiepiphysiodesis and fibular reconstruction.
The fibula is an important stabilizer of the lateral ankle. Discontinuity of the fibular shaft can lead to progressive pain and shortening of the fibula, ultimately causing loss of lateral support to the ankle. Two children, who sustained segmental bone loss of the shaft of the fibula, developed progressive symptomatic valgus of the ankle with widening of the mortice and lateral subluxation of the talus. Both patients were treated with fibular plating and grafting with tricalcium sulfate with acute reconstitution of fibular length. Distal medial tibial hemiepiphysiodesis was simultaneously performed. One patient required revision plating and grafting 14 months after the index surgery because of plate failure. The valgus angulation and the widened medial mortice were corrected in the ankles of both patients, who returned to full activities. The patients were followed to maturity; the correction has been maintained, and they remain asymptomatic. The technique used in these cases can correct valgus angulation secondary to loss of fibular congruity rather than only halting progression of the deformity.


A Combination of Conformation-Specific RAF Inhibitors Overcome Drug Resistance Brought about by RAF Overexpression.
Cancer cells often adapt to targeted therapies, yet the molecular mechanisms underlying adaptive resistance remain only partially understood. Here, we explore a mechanism of RAS/RAF/MEK/ERK (MAPK) pathway reactivation through the upregulation of RAF isoform (RAFs) abundance. Using computational modeling and in vitro experiments, we show that the upregulation of RAFs changes the concentration range of paradoxical pathway activation upon treatment with conformation-specific RAF inhibitors. Additionally, our data indicate that the signaling output upon loss or downregulation of one RAF isoform can be compensated by overexpression of other RAF isoforms. We furthermore demonstrate that, while single RAF inhibitors cannot efficiently inhibit ERK reactivation caused by RAF overexpression, a combination of two structurally distinct RAF inhibitors synergizes to robustly suppress pathway reactivation.


Identification and cloning of the genetic determinant that encodes for the K88ac adherence antigen.
Strains of Escherichia coli capable of causing diarrhea in young pigs are often able to proliferate in the upper small intestine of the infected animal due to the presence of a specific surface antigen, K88. The genetic determinants for K88 antigen production and the ability to utilize the trisaccharide raffinose (Raf) are carried on a 50-megadalton plasmid. Recombinant deoxyribonucleic acid techniques were used to insert an 8.2-megadalton HindIII fragment carrying the K88ac gene(s) from the K88/Raf plasmid pPS100 into the vector pBR322. At lease six polypeptides encoded by this fragment were expressed in minicells. These polypeptides ranged in size from 18,000 to 70,000 daltons. The K88ac antigenic subunit, which has an apparent molecular weight of 23,500, was identified by immunoprecipitation with staphylococcal protein A as the coprecipitant.


Toxoplasma gondii: expression of GRA1 gene in endoplasmic reticulum promotes both growth and adherence and modulates intracellular calcium release in macrophages.
In this study, effects of GRA1 organelle-targeted expression on macrophage functions were investigated. The recombinant plasmid pCMV/myc/ER-GRA1 was constructed and then was transfected into murine macrophage RAW264.7 by Lipofectamine, selected by resistance of G418. The selected mono-clone cell line was named ER-GRA1-RAW264.7. The expression of GRA1 was localized in ER of ER-GRA1-RAW264.7 cells by indirect immunofluorescence detection. GRA1 mRNA expression level in ER-GRA1-RAW264.7 cell was significantly enhanced with a concomitant increase in its growth and adherence activity. Fluorescence intensity of intracellular calcium in ER-GRA1-RAW264.7, ER-ctrl-RAW264.7 and RAW264.7 cells in the presence of 1 mmol/l arachidonic acid (AA) were assayed by confocal microscopy using calcium-sensitive dye, Fluo-3 AM. Cytoplasm [Ca2+]i peaked at about 18 s after AA treatment, and cytoplasm [Ca2+]i of RAW264.7 cell almost instantly stepped up after AA was added, and peaked in 3 s, with a minor cytoplasm [Ca2+]i vibration subsequently. These results demonstrated that the expression of GRA1 in ER of macrophages promotes both growth and adherence of macrophages and modulates the intracellular calcium release stimulated by AA.


IMRT reirradiation of head and neck cancer-disease control and morbidity outcomes.
Institutional and cooperative group experience has demonstrated the feasibility of reirradiation for head and neck cancer. Limited data are available regarding the use of intensity-modulated radiotherapy (IMRT) for this indication. We reviewed our initial experience using IMRT for previously irradiated head and neck cancer patients. Records of 78 consecutive patients reirradiated with IMRT for head and neck cancer between 1999 and 2004 were reviewed; 74 cases were analyzed. Reirradiation was defined as any overlap between original and new radiation treatment volumes regardless of the time interval between initial and subsequent treatment. Severe reirradiation-related toxicity was defined as toxic events resulting in hospitalization, corrective surgery, or patient death. Longitudinal estimates of survival were calculated by Kaplan-Meier technique. Twenty (27%) patients underwent salvage surgical resection and 36 (49%) patients received chemotherapy. Median follow-up from reirradiation was 25 months. Median time interval between initial radiation and reirradiation was 46 months. Median reirradiation dose was 60 Gy. Median lifetime radiation dose was 116.1 Gy. The 2-year overall survival and locoregional control rates were 58% and 64%, respectively. Severe reirradiation related toxicity occurred in 15 patients (20%); one treatment-related death was observed. The use of IMRT for reirradiation of recurrent or second primary head and neck cancers resulted in encouraging local control and survival. Reirradiation-related morbidity was significant, but may be less severe than previously published reports using conventional techniques.


Incidence and prognostic value of eosinophilia in chronic graft-versus-host disease after nonmyeloablative hematopoietic cell transplantation.
Data from a number of cohorts indicate that eosinophilia (Eo) could be associated with better outcomes following allogeneic hematopoietic cell transplant (HCT). However, little is known about its significance and prognostic value in chronic graft-versus-host disease (cGVHD) after nonmyeloablative (NMA) transplantation. Data were collected from 170 patients who underwent HCT using the same preparative regimen and GVHD prophylaxis. Donors were 6/6 HLA-matched siblings and stem cell source was peripheral blood. An eosinophil count of ≥0.5 × 10(9)/L was defined as Eo. Patients were transplanted mainly for lymphoproliferative disorders. Median age and follow-up were 54 years and 58 months, respectively. Incidents of grade II-IV acute GVHD (aGVHD) and cGVHD were 8.2% and 81.2%. Median time from HCT to cGVHD diagnosis was 142 days. Organs involved were: mouth in 80% of patients, skin in 75%, liver in 57%, eyes in 37%, gut in 14%, lungs in 5%, others in 5%. Eo was found in 44% of patients at diagnosis of cGVHD (range: 0.5-4.4 × 10(9)/L). Median time between first appearance of Eo and diagnosis of cGVHD was 4.5 days. We found no correlation between organ involvement and Eo but a lower prevalence of Eo in cGVHD associated with thrombocytopenia (P = .023). Nevertheless, we observed no association among Eo and overall survival (OS), relapse incidence, or nonrelapse mortality (NRM) in the overall cohort, nor in subsets of patients with multiple myeloma and follicular non-Hodgkin lymphoma. Although Eo is observed frequently in cGVHD following NMA transplantation, we report no correlation beween Eo and outcome.


Identifying disease trajectories with predicate information from a knowledge graph.
Knowledge graphs can represent the contents of biomedical literature and databases as subject-predicate-object triples, thereby enabling comprehensive analyses that identify e.g. relationships between diseases. Some diseases are often diagnosed in patients in specific temporal sequences, which are referred to as disease trajectories. Here, we determine whether a sequence of two diseases forms a trajectory by leveraging the predicate information from paths between (disease) proteins in a knowledge graph. Furthermore, we determine the added value of directional information of predicates for this task. To do so, we create four feature sets, based on two methods for representing indirect paths, and both with and without directional information of predicates (i.e., which protein is considered subject and which object). The added value of the directional information of predicates is quantified by comparing the classification performance of the feature sets that include or exclude it. Our method achieved a maximum area under the ROC curve of 89.8% and 74.5% when evaluated with two different reference sets. Use of directional information of predicates significantly improved performance by 6.5 and 2.0 percentage points respectively. Our work demonstrates that predicates between proteins can be used to identify disease trajectories. Using the directional information of predicates significantly improved performance over not using this information.


Glioblastoma multiforme with epithelial differentiation: a potential diagnostic pitfall in cerebrospinal fluid cytology.
Cerebrospinal fluid (CSF) cytology provides valuable diagnostic and prognostic information for diseases of the central nervous system (CNS) and remains the gold standard for the detection of neoplastic meningitis. Metastatic involvement of the CSF by non-CNS neoplasms far surpasses that of primary brain tumors, although conventional glioblastoma multiforme (GBM) can occasionally be identified in the CSF. GBM with epithelial differentiation is an uncommon variant that may contain features such as adenoid structures, signet ring cells, or squamous metaplasia. Herein, we present a case of GBM with epithelial differentiation to highlight a potential diagnostic pitfall in CSF cytology. A 55-year-old man presented with neurological symptoms and a 6.4 cm left temporal lobe cystic mass. Primary resection revealed GBM with focal epithelial differentiation confirmed by cytokeratin, epithelial membrane antigen, and glial fibrillary acidic protein immunohistochemical studies. Four months following primary resection, the patient developed severe headache for which a lumbar puncture with CSF cytologic evaluation was performed. The cytospin preparation showed numerous malignant epithelioid cells with high nuclear-cytoplasmic ratio and prominent cytoplasmic vacuoles resembling metastatic carcinoma. However, the lesional cells were cytomorphologically identical to the epithelial component present in the patient's recently diagnosed GBM. This case illustrates the potential for GBM with epithelial differentiation to closely mimic metastatic carcinoma from a non-CNS site in CSF cytology, which expands the differential diagnosis and emphasizes the necessity of clinical correlation.


A Plant-Based Meal Increases Gastrointestinal Hormones and Satiety More Than an Energy- and Macronutrient-Matched Processed-Meat Meal in T2D, Obese, and Healthy Men: A Three-Group Randomized Crossover Study.
Gastrointestinal hormones are involved in regulation of glucose metabolism and satiety. We tested the acute effect of meal composition on these hormones in three population groups. A randomized crossover design was used to examine the effects of two energy- and macronutrient-matched meals: a processed-meat and cheese (M-meal) and a vegan meal with tofu (V-meal) on gastrointestinal hormones, and satiety in men with type 2 diabetes (T2D, n = 20), obese men (O, n = 20), and healthy men (H, n = 20). Plasma concentrations of glucagon-like peptide -1 (GLP-1), amylin, and peptide YY (PYY) were determined at 0, 30, 60, 120 and 180 min. Visual analogue scale was used to assess satiety. We used repeated-measures Analysis of variance (ANOVA) for statistical analysis. Postprandial secretion of GLP-1 increased after the V-meal in T2D (by 30.5%; 95%CI 21.2 to 40.7%; p < 0.001) and H (by 15.8%; 95%CI 8.6 to 23.5%; p = 0.01). Postprandial plasma concentrations of amylin increased in in all groups after the V-meal: by 15.7% in T2D (95%CI 11.8 to 19.6%; p < 0.001); by 11.5% in O (95%CI 7.8 to 15.3%; p = 0.03); and by 13.8% in H (95%CI 8.4 to 19.5%; p < 0.001). An increase in postprandial values of PYY after the V-meal was significant only in H (by 18.9%; 95%CI 7.5 to 31.3%; p = 0.03). Satiety was greater in all participants after the V-meal: by 9% in T2D (95%CI 4.4 to 13.6%; p = 0.004); by 18.7% in O (95%CI 12.8 to 24.6%; p < 0.001); and by 25% in H (95%CI 18.2 to 31.7%; p < 0.001). Our results indicate there is an increase in gut hormones and satiety, following consumption of a single plant-based meal with tofu when compared with an energy- and macronutrient-matched processed-meat meat and cheese meal, in healthy, obese and diabetic men.


[Use of flying tests for evaluating functional capabilities of pilots].
Psychophysiological parameters of 89 pilots were examined when they performed flight tasks on a trainer under normal and complicated conditions. The experiments helped to reveal a group of test subjects (11.2%) who had low capabilities and made serious errors. The results obtained suggest that psychophysiological examinations during simulated professional activity can be recommended as a method to be used for measuring adaptive and compensatory capabilities of pilots undergoing medical expertise.


Polyamine auxotrophs of Saccharomyces cerevisiae.
Strains of yeast have been constructed that are unable to synthesize ornithine and are thereby deficient in polyamine biosynthesis. These strains were used to develop a protocol for isolation of mutants blocked directly in polyamine synthesis. There were seven mutants isolated that lack ornithine decarboxylase activity; these strains exhibited greatly decreased pool levels of putrescine, spermidine, and spermine when grown in the absence of polyamines. Three of the mutants lack S-adenosylmethionine decarboxylase activity; polyamine limitation of a representative mutant resulted in an accumulation of putrescine and a decrease in spermidine and spermine. When the mutants were cultured in the absence of polyamines, a continuously declining growth rate was observed.


Improved Pharmacokinetics and Tissue Uptake of Complexed Daidzein in Rats.
The pharmacokinetic profile and tissue uptake of daidzein (DAI) was determined in rat serum and tissues (lungs, eyes, brain, heart, spleen, fat, liver, kidney, and testes) after intravenous and intraperitoneal administration of DAI in suspension or complexed with ethylenediamine-modified γ-cyclodextrin (GCD-EDA/DAI). The absolute and relative bioavailability of DAI suspended (20 mg/kg i.v. vs. 50 mg/kg i.p.) and complexed (0.54 mg/kg i.v. vs. 1.35 mg/kg i.p.) was determined. After i.p. administration, absorption of DAI complexed with GCD-EDA was more rapid (tmax = 15 min) than that of DAI in suspension (tmax = 45 min) with a ca. 3.6 times higher maximum concentration (Cmax = 615 vs. 173 ng/mL). The i.v. half-life of DAI was longer in GCD-EDA/DAI complex compared with DAI in suspension (t0.5 = 380 min vs. 230 min). The volume of distribution of DAI given i.v. in GCD-EDA/DAI complex was ca. 6 times larger than DAI in suspension (38.6 L/kg vs. 6.2 L/kg). Our data support the concept that the pharmacokinetics of DAI suspended in high doses are nonlinear. Increasing the intravenous dose 34 times resulted in a 5-fold increase in AUC. In turn, increasing the intraperitoneal dose 37 times resulted in a ca. 2-fold increase in AUC. The results of this study suggested that GCD-EDA complex may improve DAI bioavailability after i.p. administration. The absolute bioavailability of DAI in GCD-EDA inclusion complex was ca. 3 times greater (F = 82.4% vs. 28.2%), and the relative bioavailability was ca. 21 times higher than that of DAI in suspension, indicating the need to study DAI bioavailability after administration by routes other than intraperitoneal, e.g., orally, subcutaneously, or intramuscularly. The concentration of DAI released from GCD-EDA/DAI inclusion complex to all the rat tissues studied was higher than after administration of DAI in suspension. The concentration of DAI in brain and lungs was found to be almost 90 and 45 times higher, respectively, when administered in complex compared to the suspended DAI. Given the nonlinear relationship between DAI bioavailability and the dose released from the GCD-EDA complex, complexation of DAI may thus offer an effective approach to improve DAI delivery for treatment purposes, for example in mucopolysaccharidosis (MPS), allowing the reduction of ingested DAI doses.


Historical relationship between performance assessment for radioactive waste disposal and other types of risk assessment.
This article describes the evolution of the process for assessing the hazards of a geologic disposal system for radioactive waste and, similarly, nuclear power reactors, and the relationship of this process with other assessments of risk, particularly assessments of hazards from manufactured carcinogenic chemicals during use and disposal. This perspective reviews the common history of scientific concepts for risk assessment developed until the 1950s. Computational tools and techniques developed in the late 1950s and early 1960s to analyze the reliability of nuclear weapon delivery systems were adopted in the early 1970s for probabilistic risk assessment of nuclear power reactors, a technology for which behavior was unknown. In turn, these analyses became an important foundation for performance assessment of nuclear waste disposal in the late 1970s. The evaluation of risk to human health and the environment from chemical hazards is built on methods for assessing the dose response of radionuclides in the 1950s. Despite a shared background, however, societal events, often in the form of legislation, have affected the development path for risk assessment for human health, producing dissimilarities between these risk assessments and those for nuclear facilities. An important difference is the regulator's interest in accounting for uncertainty.


Spermatic Cord Sarcoma: A 20-Year Single-Institution Experience.
Introduction: Spermatic cord sarcomas represent a rare genitourinary malignancy with a challenging diagnostic and therapeutic pathway. Different histotypes have been described and prognostic factors remain poorly defined due to the paucity of data presented in literature. Methods: Retrospective chart review of 22 adult patients treated for spermatic cord sarcoma in a single institution in the last 20 years was performed. Clinicopathological characteristics of the tumors were collected with primary and subsequent treatment. Survival analysis was performed in order to identify prognostic factors of disease-specific survival. Results: The median age at diagnosis was 68 years (58-78), the most common histotype was liposarcoma (14/22), and most patients (63.6%) were found to have positive surgical margins after surgery. The 5-year cancer specific survival was 91.3%. Grading (p = 0.480), histotype (p = 0.327), and type of intervention (p = 0.732) were not associated with survival. All patients dead of disease had positive surgical margins (p = 0.172). Conclusion: We report a good prognosis at 5 years. Wide radical resection remains the first and probably the most important step; thus, according also to literature, negative surgical margins should be aimed.


Social approaches to COVID-19 pandemic response: effectiveness and practicality in sub-Saharan Africa.
the threat of the coronavirus disease 2019 (COVID-19) pandemic to health systems and communities in sub-Saharan Africa (SSA) is enormous. Social approaches such as distancing measures are essential components of the public health response to respiratory-related infectious disease outbreaks. Due to socio-economic and broader peculiarities of SSA countries, social approaches that were effective elsewhere may have limited practicality in these contexts, and if practical; may yield different or even adverse results. We highlighted the effectiveness of these social approaches and their practicality in SSA. we conducted a comprehensive literature search through multiple databases, to identify articles relevant to social distancing. Findings were thematically summarized. our review found emerging and varying empirical evidence on the effectiveness of social approaches in the control and mitigation of the COVID-19 pandemic; thus, limiting its applicability in SSA contexts. Nonetheless, our review demonstrates that the effectiveness and practicality of social approaches in SSA contexts will depend on available resources; timing, duration, and intensity of the intervention; and compliance. Weak political coordination, anti-science sentiments, distrust of political leaders and limited implementation of legal frameworks can also affect practicality. to overcome these challenges, tailoring and adaptation of these measures to different but unique contexts for maximum effectiveness, and investment in social insurance mechanisms, are vital.


Randomised feasibility trial of pre-exposure rabies vaccination with DTP-IPV in infants.
Pre-exposure vaccination against rabies generally simplifies treatment and could be especially beneficial to children in countries where the disease is enzootic. We studied the feasibility of administering to infants pre-exposure rabies vaccination with combined diphtheria, tetanus, whole-cell pertussis, and inactivated poliomyelitis vaccine (DTP-IPV). 84 Vietnamese infants were randomly assigned to groups that received three doses of DTP-IPV vaccine at 2, 3, and 4 months of age alone (n = 43) or with two doses of purified Vero cell rabies vaccine (PVRV) at 2 and 4 months (n = 41). The safety and immunogenicity data of the groups were compared. All infants in both groups developed protective antibody concentrations against diphtheria, tetanus, pertussis, and polio. All infants who received the PVRV vaccine developed protective antibody concentrations against rabies. No serious adverse effects were reported, nor did systemic reactions differ between groups. Administration of PVRV with DTP-IPV proved safe, and elicited what are presumed to be protective antibody concentrations to all antigens in all 41 infants. Confirmation of these results could lead to integration of pre-exposure rabies vaccination into Expanded Programme on Immunisation (EPI) sessions in selected countries where rabies is enzootic.


Pathological Response of Northern Bobwhites to Oxyspirura petrowi Infections.
The effects of Oxyspirura petrowi infections in northern bobwhites ( Colinus virginianus ) are not well understood. While studies have reported O. petrowi infections, none has histopathologically examined the eye surface and intraorbital glands to assess cellular-level impacts associated with infection. This study is the first to document the histopathology associated with O. petrowi infections. Oxyspirura petrowi occurred on the eye surface as well as in the conjunctiva, lacrimal ducts, lacrimal glands, and Harderian glands. Histopathology showed infections of O. petrowi caused cellular damage to these tissues, scarring and interstitial keratitis of the cornea, and acinar atrophy of the Harderian gland.


Sex differences in the heritability of resilience.
We examine the heritability of psychological resilience among US adults aged 25 to 74 years. Using monozygotic and same sex dizygotic twin pairs from the National Survey of Mid-Life Development in the United States (MIDUS) we show that positive affect is equally heritable among men (h2 = .60) and women (h2 = .59). We then estimate the heritability of positive affect after controlling for an exhaustive list of social and inter-personal stressors, and we operationalize the residual for positive affect as resilience. According to this specification, the heritability of resilience is higher among men (h2 = .52) compared to women (h2 = .38). We show that self-acceptance is one of the most important aspects of psychological functioning that accounts for the heritability of resilience among both men and women. However, compared to women, men appear to derive additional benefits from environmental mastery that may enable otherwise sex-neutral resilient tendencies to manifest.


Acyl-CoA synthetase and the peroxisomal enzymes of beta-oxidation in human liver. Quantitative analysis of their subcellular localization.
The presence of acyl-CoA synthetase (EC 184.108.40.206) in peroxisomes and the subcellular distribution of beta-oxidation enzymes in human liver were investigated by using a single-step fractionation method of whole liver homogenates in metrizamide continuous density gradients and a novel procedure of computer analysis of results. Peroxisomes were found to contain 16% of the liver palmitoyl-CoA synthetase activity, and 21% and 60% of the enzyme activity was localized in mitochondria and microsomal fractions respectively. Fatty acyl-CoA oxidase was localized exclusively in peroxisomes, confirming previous results. Human liver peroxisomes were found to contribute 13%, 17% and 11% of the liver activities of crotonase, beta-hydroxyacyl-CoA dehydrogenase and thiolase respectively. The absolute activities found in peroxisomes for the enzymes investigated suggest that in human liver fatty acyl-CoA oxidase is the rate-limiting enzyme of the peroxisomal beta-oxidation pathway, when palmitic acid is the substrate.


Nuclear translocation of the tumor marker pyruvate kinase M2 induces programmed cell death.
Cancer cells often fail to respond to stimuli that normally activate their intrinsic apoptotic machinery. Moreover, they are able to adapt to hypoxia by changing their glycolytic rate. Pyruvate kinase (PK) is a rate-limiting enzyme in glycolysis that is converted to a less active dimer form of PKM2 isoenzyme during oncogenesis. Here, we show that both somatostatin and the structural analogue TT-232 interact with the PKM subtype. We further show that the PKM2 is translocated to the nucleus in response to TT-232 and different apoptotic agents. Nuclear translocation of PKM2 is sufficient to induce cell death that is caspase independent, isoform specific, and independent of its enzymatic activity. These results show that the tumor marker PKM2 plays a general role in caspase-independent cell death of tumor cells and thereby defines this glycolytic enzyme as a novel target for cancer therapy development.


Archaeometric study of execution techniques of white Attic vases: the case of the Perseus crater in Agrigento.
The white ground crater by the Phiale Painter (450-440 BC) exhibited in the "Pietro Griffo" Archaeological Museum in Agrigento (Italy) depicts two scenes from Perseus myth. The vase is of utmost importance to archaeologists because the figures are drawn on a white background with remarkable daintiness and attention to detail. Notwithstanding the white ground ceramics being well documented from an archaeological and historical point of view, doubts concerning the compositions of pigments and binders and the production technique are still unsolved. This kind of vase is a valuable rarity, the use of which is documented in elitist funeral rituals. The study aims to investigate the constituent materials and the execution technique of this magnificent crater. The investigation was carried out using non-destructive and non-invasive techniques in situ. Portable X-ray fluorescence and Fourier-transform total reflection infrared spectroscopy complemented the use of visible and ultraviolet light photography to get an overview and specific information on the vase. The XRF data were used to produce false colour maps showing the location of the various elements detected, using the program SmART_scan. The use of gypsum as the material for the white ground is an important result that deserves to be further investigated in similar vases.


Investigating the hygiene hypothesis as a risk factor in pediatric onset Crohn's disease: a case-control study.
Evidence for the hygiene hypothesis in the etiology of Crohn's disease (CD) is unclear. We investigated the relationship between infection-related exposures and risk for CD in children. A hospital-based case-control was carried out. Newly-diagnosed cases of CD (n = 194), less than 20 yr of age were recruited from the gastroenterology clinic of a large-pediatric inflammatory bowel disease (IBD) center in Montreal, Canada. Orthopedic patients pair-matched (n = 194) for timing of diagnosis and area of residence were recruited as controls. Information on infection-related exposures between birth and disease diagnosis was ascertained by administering a structured questionnaire to the mother and the index subject. The relationship between the frequency and timing of infection-related exposures with CD was studied. The mean age (SD) at diagnosis was 12.3 (5.1). CD was more common after 10 yr of age. Gender distribution was similar between comparison groups. In multivariate conditional logistic regression, family history of IBD (odds ratio (OR) = 4.6; 95% confidence interval (CI) = 1.6-13.3), age (OR = 1.2; 95% CI = 1.1-1.3), and owning a pet (OR = 2.0; 95% CI = 0.9-4.5) were associated with risk for CD, whereas regular use of a personal towel (OR = 0.5; 95% CI = 0.2-0.9) and lesser crowding in homes (OR = 0.3; 95% CI = 0.1-0.8) were protective. Day-care attendance during the first 6 months of life and "physician-diagnosed infections" between 5 and 10 yr of age were associated with increased risks for CD. Infection-related exposures seem to enhance risk for CD in children. The timing of these exposures during early childhood may be relevant to the etiology of pediatric CD.


Characteristics Associated With Purchasing Sugar-Sweetened Beverages and Bottled Water Among US Households, 2015.
Frequent intake of sugar-sweetened beverages (SSBs) among US adults is a public health concern because it has been associated with increased risks for adverse health outcomes such as obesity, type 2 diabetes, and cardiovascular disease. In contrast, drinking plain water (such as tap, bottled, or unsweetened sparkling water) instead of drinking SSBs might provide health benefits by improving diet quality and helping prevent chronic diseases. However, there is limited information on estimated expenditures on SSBs or bottled water among US households. This study examined differences in SSB and bottled water purchasing according to household and geographic area characteristics and estimated costs spent on purchasing SSB and bottled water from retail stores among a nationally representative sample of US households. This study is a secondary analysis of the 2015 Circana (formerly Information Resources Inc) Consumer Network Panel data, which were merged with the US Department of Agriculture nutrition data using the US Department of Agriculture Purchase-to-Plate Crosswalk-2015 dataset (the latest available version of the Purchase-to-Plate Crosswalk at the time the study began), and the Child Opportunity Index 2.0 data. A total of 63,610 households, representative of the contiguous US population, consistently provided food and beverage purchase scanner data from retail stores throughout 2015. The included demographic and socioeconomic variables were household head's age, marital status, highest education level, race and ethnicity of the primary shopper in the household, family income relative to the federal poverty level, and presence of children in the household. In addition, descriptors of households' residential areas were included, such as the county-level poverty prevalence, urbanization, census region, and census tract level Child Opportunity Index. Annual per capita spending on SSB and bottled water and daily per capita SSB calories purchased. Unadjusted and multivariable adjusted mean values of the main outcome measures were compared by household demographic, socioeconomic, and geographic characteristics using linear regression analysis including Circana's household projection factors. Nearly all households reported purchasing SSBs at least once during 2015 and spent on average $47 (interquartile range = $20) per person per year on SSBs, which corresponded to 211 kcal (interquartile range = 125 kcal) of SSBs per person per day. About seven in 10 households reported purchasing bottled water at least once during 2015 and spent $11 (interquartile range = $5) per person on bottled water per year. Both annual per capita SSB and bottled water spending, and daily per capita SSB calories purchased was highest for households whose heads were between 40 and 59 years of age, had low household income, or lived in poor counties, or counties with a low Child Opportunity Index. Annual per capita spending was also higher for households with never married/widowed/divorced head, or at least 1 non-Hispanic Black head, and households without children, or those living in the South. Daily per capita SSB calorie purchases were highest for households where at least 1 head had less than a high school degree, households with at least 1 Hispanic or married head, and households with children or those living in the Midwest. These findings suggest that households that had lower socioeconomic status had higher annual per capita spending on SSBs and bottled water and higher daily per capita total SSB calories purchased than households with higher socioeconomic status.