Serum-to-saliva transfer of the immunoreactive insulin (IRI) in children with obesity associated with insulin-resistance.
Assuming that the serum-to-saliva transfer of insulin reflects internalization and re-cycling of the hormone in the membrane-located binding sites of salivary epithelial cells and that these cells have in obesity a'marked decrease in insulin receptor content, it has been postulated that insulin resistance in infantile obesity can be detected by the changes in the salivary immunoreactive insulin during the oral glucose tolerance test (OGTT). The study included 31 obese children and adolescents of both sexes, subjected to OGTT. Samples of blood and saliva were collected at 30, 60, 120, 180 and 240 minutes for determinations of glucose and IRI. The blood glucose values were generally normal whereas IRI was excessively high. The dynamics of salivary IRI was similar (easy peak followed by slow descent) with the mean serum values but lower by about two-thirds, and the peak was 30-60 minutes delayed. The serum IRI values correlated significantly with the saliva ones at all time-intervals except for the 30-minute ones. The serum IRI values were significantly lower at the 30-minute time interval, whereas the salivary IRI were the lowest (and of borderline significance) at the 60-min. time interval. The mean glucose/kg doses given orally were not significantly different in the two groups. It was concluded that a hormonal activity detectable by IRI assay through the PEG separation method does exist, with a concomitant variation of serum-to-saliva transfer as shown by the OGTT test. It was also concluded that since the salivary values are lower, the direction of the flow is from serum to saliva and not the reverse. Finally, on the basis of our data, an "in situ" synthesis of insulin (hormonogenic exocrinism) can not be ruled out.


Keys to effective third-party process safety audits.
The Occupational Safety and Health Administration's (OSHA's) Process Safety Management (PSM) regulation was promulgated in 1992. The U.S. Environmental Protection Agency's (EPA's) corresponding Risk Management Program (RMP) rule followed in 1996. Both programs include requirements for triennial compliance audits. Effective compliance audits are critical in identifying program weaknesses and ensuring the safety of facility personnel and the surrounding public. Large companies with corporate and facility health, safety, and environmental groups typically have the resources and experience to conduct audits internally, either through a corporate audit team or the sharing of personnel between multiple facilities. Small to medium sized businesses frequently do not have the expertise or the resources to perform compliance audits, and rely on third-party consultants to provide these services. This paper will discuss the observations of the authors in performing audits and working with PSM/RMP programs across a number of market sectors (e.g. chemical, petrochemical, pharmaceutical, food and beverage, water treatment), including effective practices, hurdles to successful implementation and execution of programs, and typical program shortcomings. The paper will also discuss steps to improve the audit process and increase effectiveness whether performed by a third party or internally.


[Experience of Nurses in Charge of COVID-19 Screening at General Hospitals in Korea].
The purpose of this study was to understand and describe the experiences of nurses in charge of COVID-19 screening at general hospitals in South Korea. Data were collected through individual in-depth interviews with 14 nurses who had been working for more than a month at a screening clinic operated by two general hospitals from May 11 to July 20, 2021. Verbatim transcripts were analyzed using Colaizzi's phenomenological analysis. As a result of analysis, four theme clusters were extracted from nurses' experiences, as follow: the role of the hospital gatekeeper entrusted with managing the COVID-19 pandemic, struggling to maintain the protective barrier, boundlessness like a Mobius strip, and driving force to endure as a nurse in charge of COVID-19 screening. The results of this study provide a deeper understanding of the lives of screening clinic nurses who are struggling with the COVID-19 situation. The results are expected to be useful in providing basic data for improving the infection control system and response strategies that can be applied to nursing practice in other pandemic situations.


Chronic cannabis use is associated with impaired fear extinction in humans.
The use of fear conditioning and extinction paradigms to examine intermediate phenotypes of anxiety and stress-related disorders has facilitated the identification of neurobiological mechanisms that underlie specific components of abnormal psychological functioning. Across species, acute pharmacologic manipulation of the endogenous cannabinoid system has provided evidence of its critical role in fear extinction, but the effects of chronic cannabis on extinction are relatively understudied. In rats, chronic cannabinoid administration impairs fear extinction in a drug-free state. Here we examine whether chronic cannabis use is associated with impaired fear extinction in humans. Participants were healthy chronic cannabis users (n = 20) and nonuser controls with minimal lifetime cannabis use (n = 20) matched on age, sex, and race who all screened negative for psychiatric disorders. A 2-day differential fear conditioning paradigm was used to test the hypothesis that chronic cannabis use would be associated with impaired extinction of the skin conductance response. Consistent with hypotheses, chronic cannabis use was associated with reduced within-session extinction of skin conductance response on Day 1 (d = 0.78), and between-session extinction on Day 2 (d = 0.76). Unexpectedly, cannabis use was also associated with reduced subjective differentiation between threat and safety stimuli during conditioning. Replication and translation of findings are necessary to test potential mechanisms directly and examine whether impairments can be reversed pharmacologically or after a period of cannabis abstinence. (PsycINFO Database Record


Understanding the combined effects of multiple stressors: A new perspective on a longstanding challenge.
Wildlife populations and their habitats are exposed to an expanding diversity and intensity of stressors caused by human activities, within the broader context of natural processes and increasing pressure from climate change. Estimating how these multiple stressors affect individuals, populations, and ecosystems is thus of growing importance. However, their combined effects often cannot be predicted reliably from the individual effects of each stressor, and we lack the mechanistic understanding and analytical tools to predict their joint outcomes. We review the science of multiple stressors and present a conceptual framework that captures and reconciles the variety of existing approaches for assessing combined effects. Specifically, we show that all approaches lie along a spectrum, reflecting increasing assumptions about the mechanisms that regulate the action of single stressors and their combined effects. An emphasis on mechanisms improves analytical precision and predictive power but could introduce bias if the underlying assumptions are incorrect. A purely empirical approach has less risk of bias but requires adequate data on the effects of the full range of anticipated combinations of stressor types and magnitudes. We illustrate how this spectrum can be formalised into specific analytical methods, using an example of North Atlantic right whales feeding on limited prey resources while simultaneously being affected by entanglement in fishing gear. In practice, case-specific management needs and data availability will guide the exploration of the stressor combinations of interest and the selection of a suitable trade-off between precision and bias. We argue that the primary goal for adaptive management should be to identify the most practical and effective ways to remove or reduce specific combinations of stressors, bringing the risk of adverse impacts on populations and ecosystems below acceptable thresholds.


Comparison of pain properties in fibromyalgia patients and rheumatoid arthritis patients.
Pain properties of 50 fibromyalgia patients were examined and compared with pain properties of 50 rheumatoid arthritis patients. In both fibromyalgia and rheumatoid arthritis, pain was bilateral, involved multiple sites, and was of equal intensity (60.8 versus 58.7, respectively, on a scale of 100). Fibromyalgia pain, however, was less localized to the joints and suggested greater spatial diffusion. It involved more kinds of pain experiences (radiating, steady, spreading, spasms, gnawing, unlocalized, pricking, crushing, shooting, pressing, splitting, cramping, nagging, and pins and needles), and was dispersed over larger areas of the body. The anatomic sites best for discrimination between patients with fibromyalgia and patients with rheumatoid arthritis were the lower back, thigh, abdomen, head, and hips for fibromyalgia, and wrist, foot, and fingers for rheumatoid arthritis. The traditional clinical description of aching and stiffness does not appear to accurately describe the complexity of the fibromyalgia pain syndrome.


Development of neutralizing antibodies and group A common antibodies against natural infections with human rotavirus.
We determined the levels of group A common and neutralizing antibodies against human rotavirus in paired serum specimens obtained from 38 infants within 12 days of the onset of diarrhea. Thirty of the infants excreted rotavirus in stools, and eight did not. Nine patients (30%) with rotavirus diarrhea and seven patients (88%) with diarrhea due to other causes had detectable levels (greater than or equal to 1: 80) of immunoglobulin (IgG) common antibodies in acute-phase sera. All the patients with rotavirus diarrhea showed at least fourfold rises in titers of IgG or IgM common antibodies or both, while only two control patients showed significant rises in either IgG or IgM common antibodies in their convalescent-phase sera. Of the 19 patients excreting "short" electropherotypes of rotavirus, 18 showed at least fourfold rises in titers of neutralizing antibodies against serotype 2 human rotavirus but not against serotype 1, 3, or 4. Nine of the ten patients excreting "long" electropherotypes showed significant rises in neutralizing antibodies against serotype 3, and the other patient showed a significant rise in neutralizing antibodies against serotype 1. One patient excreted long and short electropherotypes simultaneously, and he also showed a significant rise in neutralizing antibodies against serotype 2 and 3 viruses. The control patients with diarrhea did not show significant changes in titers of antibodies against any of the serotypes. These results demonstrated that the neutralizing antibody response within 2 weeks after clinical onset is specific for the infecting serotype of rotavirus.


Understanding of Pathophysiology and Optimal Treatment for Anterior Circulation Large Vessel Occlusion beyond 24 h from Onset of Stroke.
We report three cases in which endovascular treatment (EVT) was performed for anterior circulation large vessel occlusion (LVO) beyond 24 h from the onset of stroke. Case 1 experienced left hemispatial neglect and gait disorder due to right internal cerebral artery (ICA) occlusion and underlying atherosclerosis. After percutaneous transluminal angioplasty (PTA), revascularization with mild stenosis was achieved. Case 2 complained of reduced activity, motor aphasia, and right-sided hemiparesis due to left middle cerebral artery occlusion. After thrombectomy using a retrieval stent, revascularization with M1 stenosis and distal perfusion delay was observed, which improved after PTA. Case 3 arrived at our hospital 30 h after the onset of dysarthria and gait disturbance due to left ICA occlusion. Since the symptoms were mild, medical treatment was started; however, the patient's symptoms deteriorated 6 h later, and EVT was required. After thrombectomy using a retrieval stent, revascularization was achieved. LVO pathophysiology beyond 24 h of stroke onset varies and may require multimodal treatment. Preserving the pyramidal tract may lead to favorable outcomes, even in cases of anterior circulation LVO. EVT may be effective for anterior circulation LVO because, in some patients, infarct volume continues to increase >24 h after stroke onset.


Design of Next Generation Polymyxins with Lower Toxicity: The Discovery of SPR206.
Polymyxins are an important class of antibiotics for the treatment of bacterial infections due to multidrug resistant Gram-negative pathogens. However, their clinical utility is limited by nephrotoxicity. Here, we report a series of promising next generation polymyxin nonapeptides identified on the basis of our understanding of the relationship of structure with activity, cytotoxicity, and kidney compartment accumulation. We demonstrate that nonapeptides with an amine-containing N-terminal moiety of specific regio- and stereochemistry possess superior in vitro activity, together with lower cytotoxicity compared to polymyxin B. We further demonstrate that compounds with a β-branched aminobutyrate N-terminus with an aryl substituent offer a promising combination of low cytotoxicity and kidney exposure, leading to low toxicity in the mouse. From this series, SPR206 has been selected as a development candidate.


Preoperative prognostic factors for olfactory change after functional endoscopic sinus surgery.
Functional endoscopic sinus surgery (FESS) has been considered to improve the olfactory function in patients with chronic rhinosinusitis. However, which factors might affect the olfactory outcome after FESS has not been well investigated. A total of 70 patients with chronic rhinosinusitis who underwent FESS were enrolled in the study. The potential prognostic factors for improvement in olfaction after FESS were evaluated in these patients. On the day before FESS, the olfactory function was evaluated by a symptom score, a phenyl ethyl alcohol odor detection threshold test, the University of Pennsylvania Smell Identification Test, and a short-term odor memory/discrimination test, and were reevaluated by the same methods 6 months after FESS. The degree of nasal obstruction, the second minimal cross-sectional area measured by acoustic rhinometry, computed tomography scores before FESS, the degree of preoperative olfactory loss indicated by threshold and identification scores, and coexistence of nasal polyps or allergic rhinitis were not significantly reliable to influence the rates of olfactory improvement after FESS. Degree of nasal obstruction, extent of rhinosinusitis disease, and coexistence of nasal polyps or allergic rhinitis did not predicate the overall possibility of any olfactory improvement after FESS.


Antitumor effects of cytolytic T lymphocytes (CTL) and natural killer (NK) cells in head and neck cancer.
Immune effector cells were generated in vitro and compared for activity against human head and neck cancer (HNC). A subset of human IL2-activated natural killer (A-NK) cells was able to eliminate tumor cells in vitro by necrosis, apoptosis or cytokine-mediated effects and to induce regression of established tumors in vivo, in a xenograft nude mouse model of HNC. Cytolytic T lymphocytes (CTL) with specificity for a human oral carcinoma were as effective as A-NK cells in mediating killing of autologous tumor cells or entering spheroids. Stable HNC transfectants with the human IL2 gene, which produced IL2 were implanted in nude mice. IL2-secreting tumors regressed spontaneously. Strategies available for use in immunotherapy of human HNC are being evaluated to provide a solid basis for their future therapeutic applications.


Stakeholder strategies for the physician executive.
If physician executives are to be effective in confronting the environmental turbulence and uncertainty facing their organizations, they must effectively manage their stakeholders. This article extends the stakeholder approach described in the May-June 1989 issue of Physician Executive as a tool for the physician executive in the development of practical strategies to cope with turbulence and uncertainty. We suggest four generic strategies physician executives can use: involve supportive stakeholders, monitor marginal stakeholders, defend against nonsupportive stakeholders, and collaborate with mixed-blessing stakeholders. As an overarching strategy, a physician executive should try to change the organization's relationships with a stakeholder from a less favorable category to a more favorable one. The stakeholder can then be managed using the generic strategy most appropriate for the category.


Impact of geriatric factors on surgical and prognostic outcomes in elderly patients with soft-tissue sarcoma.
Patients aged ≥65 years requiring surgery for soft-tissue sarcoma are a concern in an aging society. We aimed to reveal the association of clinical/geriatric factors with survival period or postoperative events in such patients who underwent surgery. We enrolled patients aged ≥65 years who underwent surgery for localized soft-tissue sarcoma at five institutions. We retrospectively collected clinical/geriatric factors and laboratory data, and analyzed their association with outcomes using univariate and multivariate analyses. Among the 202 patients included, mean age at presentation was 73 years. Surgical margin was R0 in 139 patients (69%). The Eastern Cooperative Oncology Group performance status was ≥2 in 15 (7%). Thirty patients (15%) showed thinness (body mass index <18.49 kg/cm2). High-sensitivity-modified Glasgow prognostic score ≥1 was seen in 52 patients (26%). Multivariate analysis showed that R1 surgical margin was significantly correlated with poor sarcoma-specific survival (hazard ratio for R1 vs. R0, 3.17; P = 0.001) and event-free survival (hazard ratio for R1 vs. R0, 2.56; P < 0.001). Higher Eastern Cooperative Oncology Group performance status was significantly associated with poor sarcoma-specific survival (hazard ratio for ≥2 vs. 0 or 1, 2.15; P = 0.038), and higher sensitivity-modified Glasgow prognostic score was significantly associated with poor event-free survival (hazard ratio for ≥1 vs. 0, 1.74; P = 0.046). Severe thinness (body mass index <16.00) was a risk factor for postoperative events (odds ratio for body mass index <16.00 vs. ≥16.00, 8.15, P = 0.010). Negative surgical margin was associated with better survival. Coexisting conditions had an impact on outcomes in elderly soft-tissue sarcoma patients.


Facile preparation of purine and pyrimidine 2-deoxy-beta-D-ribonucleosides by biotransformation on encapsulated cells.
A preparative-scale synthesis of pyrimidine or purine 2'-deoxy-beta-D-ribonucleosides from a heterocyclic base and 2'-deoxyuridine proceeds by biotransformation reaction in the presence of thymine-dependent E. coli mutant cells encapsulated in alginate gel. The products are isolated by octadecyl-silica or ion-exchange chromatography.


Evaluation of the analytical performance of the coulometry-based Optium Omega blood glucose meter: what do such evaluations show?
The article entitled "Evaluation of the Analytical Performance of the Coulometry-Based Optium Omega Blood Glucose Meter", by Solnica and colleagues in this issue of Journal of Diabetes Science and Technology demonstrates that the Optium Omega blood glucose meter meets the analytical requirements for glucose meter performance and it is stated that the results are clinically useful. The authors studied precision, bias, and reagent lot-to-lot error sources. The ultimate goal of an evaluation is to estimate the distribution of errors (from any source) that will be experienced in routine use. The data collection and analysis methods to achieve this are discussed, as are the standards used to compare the results. Claiming clinical usefulness is almost a boilerplate statement in evaluations but meeting standards does not prove clinical usefulness.


Urinary trehalase activity is a useful marker of renal proximal tubular damage in newborn infants.
To clarify the reliability of urinary trehalase activity as a marker of cellular proliferation and/or damage of renal proximal tubules, the activity was examined in healthy newborn infants or infants treated with tobramycin, a drug known as causing tubular cell damage. Eighty-one newborn infants (56 mature infants and 25 premature infants) were enrolled in the study. Urinary trehalase was examined using a spot urine sample during the first 7 days of age and on the 10th day of age. A good positive correlation was observed between urinary trehalase activity/creatinine ratio (T/Cr) on the 10th day of age and conceptional age or body weight (n = 46, r = 0.58, p < 0.001). Urinary trehalase of 29 healthy mature infants was higher during the first few days of age, after which it decreased to an almost steady level. Urinary trehalase of 6 premature infants during the first few days of age was significantly lower than that of mature infants, after which it increased and became equal to that of the mature infants on the 7th day of age. Treatment with ampicillin (100 mg/kg) and tobramycin (5 mg/kg) of 6 mature infants with pneumonia for 6 days resulted in a significant elevation of the urinary T/Cr. The extent of this elevation was greater than that of the urinary N-acetyl-beta-D-glucosaminidase (NAG) activity/creatinine ratio (NAG/Cr). A significant correlation was observed between the urinary T/Cr and the urinary NAG/Cr (r = 0.67, p < 0.01) or gamma-glutamyl transpeptidase/creatinine ratio (r = 0.48, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)


Dynamics and environment of mitochondrial water as detected by 1H NMR.
The dynamics and environment of water in suspensions of isolated rat liver mitochondria have been investigated by 1H NMR. NMR longitudinal and transversal relaxation times (T1 and T2) were measured in the resuspension medium (2.65 s and 44.57 ms) and in mitochondrial suspensions (1.74 s and 23.14 s), respectively. Results showed monoexponential relaxation in both cases, suggesting a fast water exchange across the inner mitochondrial membrane. Ferromagnetically induced shift of the extramitochondrial water with nonpermeant ferromagnetic particles revealed no detectable water signal from the intramitochondrial compartment, confirming the fast exchange case. Simulations on a two-compartment model indicated that the intramitochondrial water residence time has an upper limit of approximately 100 microseconds. Calculated intramitochondrial relaxation times revealed that the intramitochondrial environment has an apparent viscosity 30 times larger than the resuspension medium and 15 times larger than the cytosol of erythrocytes. The higher apparent viscosity of the mitochondrial matrix could account for reductions of more than one order of magnitude in the diffusion coefficient of water and other substrates, limitations in the rate of enzymatic reactions which are diffusion controlled and a more favorable formation of multienzyme complexes.


The role of CT imaging for management of COVID-19 in epidemic area: early experience from a University Hospital.
To evaluate the clinical value of the chest CT scan compared to the reference standard real-time polymerase chain reaction (RT-PCR) in COVID-19 patients. From March 29th to April 15th of 2020, a total of 240 patients with respiratory distress underwent both a low-dose chest CT scan and RT-PCR tests. The performance of chest CT in diagnosing COVID-19 was assessed with reference to the RT-PCR result. Two board-certified radiologists (mean 24 years of experience chest CT), blinded for the RT-PCR result, reviewed all scans and decided positive or negative chest CT findings by consensus. Out of 240 patients, 60% (144/240) had positive RT-PCR results and 89% (213/240) had a positive chest CT scans. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of chest CT in suggesting COVID-19 were 100% (95% CI: 97-100%, 144/240), 28% (95% CI: 19-38%, 27/240), 68% (95% CI: 65-70%) and 100%, respectively. The diagnostic accuracy of the chest CT suggesting COVID-19 was 71% (95% CI: 65-77%). Thirty-three patients with positive chest CT scan and negative RT-PCR test at baseline underwent repeat RT-PCR assay. In this subgroup, 21.2% (7/33) cases became RT-PCR positive. Chest CT imaging has high sensitivity and high NPV for diagnosing COVID-19 and can be considered as an alternative primary screening tool for COVID-19 in epidemic areas. In addition, a negative RT-PCR test, but positive CT findings can still be suggestive of COVID-19 infection.


D3 -creatine dilution for skeletal muscle mass measurement: historical development and current status.
The French chemist Michel Eugène Chevreul discovered creatine in meat two centuries ago. Extensive biochemical and physiological studies of this organic molecule followed with confirmation that creatine is found within the cytoplasm and mitochondria of human skeletal muscles. Two groups of investigators exploited these relationships five decades ago by first estimating the creatine pool size in vivo with 14 C and 15 N labelled isotopes. Skeletal muscle mass (kg) was then calculated by dividing the creatine pool size (g) by muscle creatine concentration (g/kg) measured on a single muscle biopsy or estimated from the literature. This approach for quantifying skeletal muscle mass is generating renewed interest with the recent introduction of a practical stable isotope (creatine-(methyl-d3 )) dilution method for estimating the creatine pool size across the full human lifespan. The need for a muscle biopsy has been eliminated by assuming a constant value for whole-body skeletal muscle creatine concentration of 4.3 g/kg wet weight. The current single compartment model of estimating creatine pool size and skeletal muscle mass rests on four main assumptions: tracer absorption is complete; tracer is all retained; tracer is distributed solely in skeletal muscle; and skeletal muscle creatine concentration is known and constant. Three of these assumptions are false to varying degrees. Not all tracer is retained with urinary isotope losses ranging from 0% to 9%; an empirical equation requiring further validation is used to correct for spillage. Not all tracer is distributed in skeletal muscle with non-muscle creatine sources ranging from 2% to 10% with a definitive value lacking. Lastly, skeletal muscle creatine concentration is not constant and varies between muscles (e.g. 3.89-4.62 g/kg), with diets (e.g. vegetarian and omnivore), across age groups (e.g. middle-age, ~4.5 g/kg; old-age, 4.0 g/kg), activity levels (e.g. athletes, ~5 g/kg) and in disease states (e.g. muscular dystrophies, <3 g/kg). Some of the variability in skeletal muscle creatine concentrations can be attributed to heterogeneity in the proportions of wet skeletal muscle as myofibres, connective tissues, and fat. These observations raise serious concerns regarding the accuracy of the deuterated-creatine dilution method for estimating total body skeletal muscle mass as now defined by cadaver analyses of whole wet tissues and in vivo approaches such as magnetic resonance imaging. A new framework is needed in thinking about how this potentially valuable method for measuring the creatine pool size in vivo can be used in the future to study skeletal muscle biology in health and disease.


Sustained improvement in fellows' echocardiographic completeness through the coronavirus pandemic with a standardised imaging protocol.
First-year cardiology fellows must quickly learn basic competency in echocardiography during fellowship orientation. This educational process was disrupted in 2020 due to the coronavirus pandemic, as our hands-on echocardiography teaching transitioned from practice on paediatric volunteers to simulation-based training. We previously described an improvement in echocardiographic completeness after implementation of a standardised imaging protocol for the performance of acute assessments of ventricular function. Herein, we assessed whether this improvement could be sustained over the two subsequent years, including the fellowship year affected by the pandemic. Echocardiograms performed by first-year paediatric cardiology fellows to assess ventricular function were reviewed for completeness. The frequency with which each requested component was included was measured. A total demographic score (out of 7) and total imaging score (out of 23) were calculated. The pre-protocol years (2015-2017) were compared to the post-protocol years (2018-2020), and the pre-COVID years (2018-2019) were compared to the year affected by COVID (2020). There was a sustained improvement in completeness after protocol implementation with improvement in the demographic score (median increasing from 6 to 7, p < 0.001) and imaging score (median increasing from 13 to 16, p < 0.001). More individual components showed a statistically significant increase in frequency compared to our prior publication. The COVID pandemic resulted in very few differences in completeness. Demographic reporting improved modestly (p = 0.04); the imaging score was unchanged (p = 0.59). The only view obtained less frequently was the apical two-chamber view. A standardised imaging protocol allowed sustained improvements in echocardiographic completeness despite the disruption of fellowship orientation by COVID-19.


Teat disorders predispose ewes to clinical mastitis after challenge with Mannheimia haemolytica.
In order to study the effects of sheep teat disorders on the protection of the mammary gland, we used a Mannheimia haemolytica isolate, which did not cause clinical mastitis when deposited into intact teats. In the first experiment, this was deposited into the duct of teats with orf (Group A, n=5) or papilloma (Group B, n=3). In the second, teats were chapped and then, the organism was deposited into the duct (Group C, n=7) or on the skin (Group D, n=4). Ewes with healthy teats were controls (Group E, deposition into duct, n=5; Group F, deposition on skin, n=2). The ewes in Groups A, B or C developed clinical mastitis 5 h later, whilst the ewes in Group D developed it 2 d later; no control ewe developed clinical mastitis. In ewes with teat lesions, the organism was isolated from secretion samples and the California Mastitis Test became positive 5 h after challenge; neutrophils and lymphocytes were seen in Giemsa-stained secretion films from Group A or B ewes, whilst macrophages, neutrophils and lymphocytes in films from Group C or D ewes; neutrophils were predominating in films from Group E or F ewes. Inside the teats of Group A, B, C or D ewes, folds, hyperaemia and mucosal thickness were seen; histologically, subepithelial leucocytic infiltration was seen. In Group A or B ewes, no evidence of lymphoid tissue at the teat duct-cistern border was found. In Group C or D ewes, intense erosion and ulceration of the teat skin and conspicuous lymphoid tissue at the teat duct-cistern border, were evident; lesions characteristic of haemorrhagic mastitis were in the mammary parenchyma. In control ewes, subepithelial leucocytic infiltration in the teat duct and lymphoid tissue as above, were evident. We postulate that teat lesions can be predisposing factor to mastitis, by adversely affecting defences and speeding the process of infection and making it more severe.


trans-Tetra-carbonyl-bis-[tris-(3-fluoro-phen-yl)phosphane]chromium(0).
In the title compound, [Cr(C(18)H(12)F(3)P)(2)(CO)(4)], the Cr atom is octa-hedrally coordinated by four carbonyl ligands and the two tertiary phosphanes, which are trans to each other. The three benzene rings in one phosphane ligand make dihedral angles of 53.50 (9), 75.51 (10) and 80.63 (10)° with each other, while in the other ligand these angles are 51.92 (10), 78.56 (11) and 86.80 (10)°. C-H⋯O and C-H⋯F inter-actions link the mol-ecules into a three-dimensional network. Each of the F atoms is disordered over two positions with refined occupancies of 0.944 (3):0.056 (3), 0.702 (4):0.298 (4), 0.829 (4):0.171 (4), 0.567 (4):0.433 (4), 0.545 (4):0.455 (4) and 0.920 (4):0.080 (4).


Bio-Inspired Polymeric Structures with Special Wettability and Their Applications: An Overview.
It is not unusual for humans to be inspired by natural phenomena to develop new advanced materials; such materials are called bio-inspired materials. Interest in bio-inspired polymeric superhydrophilic, superhydrophobic, and superoleophobic materials has substantially increased over the last few decades, as has improvement in the related technologies. This review reports the latest developments in bio-inspired polymeric structures with desired wettability that have occurred by mimicking the structures of lotus leaf, rose petals, and the wings and shells of various creatures. The intrinsic role of surface chemistry and structure on delivering superhydrophilicity, superhydrophobicity, and superoleophobicity has been extensively explored. Typical polymers, commonly used structures, and techniques involved in developing bio-inspired surfaces with desired wettability are discussed. Additionally, the latest applications of bio-inspired structures with desired wettability in human activities are also introduced.


T Cells Specific for a Mycobacterial Glycolipid Expand after Intravenous Bacillus Calmette-Guérin Vaccination.
Intradermal vaccination with Mycobacterium bovis bacillus Calmette-Guérin (BCG) protects infants from disseminated tuberculosis, and i.v. BCG protects nonhuman primates (NHP) against pulmonary and extrapulmonary tuberculosis. In humans and NHP, protection is thought to be mediated by T cells, which typically recognize bacterial peptide Ags bound to MHC proteins. However, during vertebrate evolution, T cells acquired the capacity to recognize lipid Ags bound to CD1a, CD1b, and CD1c proteins expressed on APCs. It is unknown whether BCG induces T cell immunity to mycobacterial lipids and whether CD1-restricted T cells are resident in the lung. In this study, we developed and validated Macaca mulatta (Mamu) CD1b and CD1c tetramers to probe ex vivo phenotypes and functions of T cells specific for glucose monomycolate (GMM), an immunodominant mycobacterial lipid Ag. We discovered that CD1b and CD1c present GMM to T cells in both humans and NHP. We show that GMM-specific T cells are expanded in rhesus macaque blood 4 wk after i.v. BCG, which has been shown to protect NHP with near-sterilizing efficacy upon M. tuberculosis challenge. After vaccination, these T cells are detected at high frequency within bronchoalveolar fluid and express CD69 and CD103, markers associated with resident memory T cells. Thus, our data expand the repertoire of T cells known to be induced by whole cell mycobacterial vaccines, such as BCG, and show that lipid Ag-specific T cells are resident in the lungs, where they may contribute to protective immunity.


Cyclin D1 Is a Ligand-independent Co-repressor for Thyroid Hormone Receptors.
Thyroid hormone receptors (TRs) are critical regulators of growth, differentiation, and homeostasis. TRs function by regulating the expression of thyroid hormone (T3) target genes in both ligand-dependent and -independent pathways. Distinct classes of co-regulatory proteins modulate these two pathways. We show here a novel role of cyclin D1 as a T3-independent co-repressor for TRs. Cyclin D1 interacted with TR in vitro and in cells in a ligand-independent manner. Cyclin D1 acted to repress both the silencing activity of the unliganded TR and the transcriptional activity of the liganded TR. The repression was not due to the inhibition of the binding of TR to the thyroid hormone response element but by serving as a ligand-independent bridging factor to selectively recruit HDAC3 to form ternary complexes. The repression was augmented by increasing expression of HDAC3 but not by HDAC1 and was alleviated by trichostatin A. Thus, cyclin D1 is a novel ligand-independent co-repressor that opens a new paradigm to understand the molecular basis of the silencing action of TR.


Female upper body and breast skin temperature and thermal comfort following exercise.
Breast support reduces breast pain and movement during exercise, however, an extra layer of clothing may affect thermoregulation. This preliminary study investigated female upper body and breast skin temperature and thermal comfort following short-duration exercise. Eight female participants with C-cup breasts had thermal images (infra-red camera, FLIR systems) of the bare breasts, the breasts in two sports bras (composite and polyester) and the abdomen, taken before and after 20 min of exercise at 28(o)C. Following exercise, bare-breast, bra and abdomen temperatures reduced by 0.61(o)C, 0.92(o)C and 2.06(o)C, respectively. The polyester sports bra demonstrated greater thermal comfort and enabled a greater change in skin temperature than the composite sports bra. It is concluded that following short-duration exercise, sports bras reduced the cooling ability of the breast. Material properties of the bras affect thermal comfort and post-exercise skin temperature; this should be an important consideration for sports bra manufacturers. This study investigates the effect of sports bras on thermal regulation of the breast following exercise. Sports bras negatively affected the cooling ability of the skin on the breast, with the material properties of the bra affecting thermal comfort following exercise. These results present important considerations for sports bra manufacturers.


Adolescent with Superior Mesenteric Artery Syndrome.
The underlying etiologies of paediatric bowel obstruction are wide ranging. It can be divided into proximal and distal bowel obstruction. Amongst the different etiologies of the proximal bowel obstructions at the level of the duodenum, there are a few etiologies including duodenal atresia, internal hernias, intestinal malrotation, annular pancreas etc. Superior mesenteric artery syndrome is amongst one of these differential diagnoses which is more prevalent in the adolescent age group. We describe the imaging features of this entity and its demographics, imaging characteristics, treatment and prognosis.


The Implicit Association Test as a tool for studying dysfunctional associations in psychopathology: strengths and limitations.
Dysfunctional beliefs and associations are assumed to play a crucial role in various forms of psychopathology. Recently, it has been suggested that the Implicit Association Test (IAT) provides a better way to assess those associations than traditional self-report measures. During the IAT, participants classify items as belonging to one of four concepts. Results show that performance is superior when associated concepts are assigned to the same response than when associated concepts are assigned to different responses. I present an overview of the available literature on the IAT and evaluate the usefulness of this task as a tool for clinically oriented research.


Hemangioma - A pointer to Abernethy syndrome?
Diffuse pulmonary arteriovenous malformations or pulmonary arterial hypertension (PAH) may result from congenital portosystemic venous shunts. Hemangioma as a physical sign of congenital portosystemic shunts (like Abernethy syndrome) has not been described. I report two children (one with severe cyanosis from pulmonary arteriovenous malformations and the other with severe PAH) with cutaneous hemangioma and Abernethy syndrome. Hemangioma may be a clinical pointer to portosystemic shunts even in the absence of obvious liver disease.


In Vivo pH Regulation by a Na/H Antiporter in the Halotolerant Alga Dunaliella salina.
Na(+)/H(+) exchange activity in whole cells of the halotolerant alga Dunaliella salina can be elicited by intracellular acidification due to addition of weak acids at appropriate external pH. The changes in both intracellular pH and Na(+) were followed. Following a mild intracellular acidification, intracellular Na(+) content increased dramatically and then decreased. We interpret the phase of Na(+) influx as due to the activation of the plasma membrane Na(+)/H(+) antiporter and the phase of Na(+) efflux as due to an active Na(+) extrusion process. The following observations are in agreement with this interpretation: (a) the Na(+) influx phase was sensitive to Li(+), which is an inhibitor of the Na(+)/H(+) antiporter, did not require energy, and was insensitive to vanadate; (b) the Na(+) efflux phase is energy-dependent and sensitive to the plasma membrane ATPase inhibitor, vanadate. Following intracellular acidification, a drastic decrease in the intracellular ATP content is observed that is reversed when the cells regain their neutral pH value. We suggest that the intracellular acidification-induced change in the internal Na(+) concentration is due to a combination of Na(+) uptake via the Na(+)/H(+) antiporter and an active, ATPase-dependent, Na(+) extrusion. The Na(+)/H(+) antiporter seems, therefore, to play a principal role in internal pH regulation in Dunaliella.


The role of sunlight exposure in determining the vitamin D status of the U.K. white adult population.
Vitamin D is necessary for bone health and is potentially protective against a range of malignancies. Opinions are divided on whether the proposed optimal circulating 25-hydroxyvitamin D [25(OH)D] level (≥ 32 ng mL⁻¹) is an appropriate and feasible target at population level. We examined whether personal sunlight exposure levels can provide vitamin D sufficient (≥ 20 ng mL⁻¹) and optimal status in the U.K. public. This prospective cohort study measured circulating 25(OH)D monthly for 12 months in 125 white adults aged 20-60 years in Greater Manchester. Dietary vitamin D and personal ultraviolet radiation (UVR) exposure were assessed over 1-2 weeks in each season. The primary analysis determined the post-summer peak 25(OH)D required to maintain sufficiency in wintertime. Dietary vitamin D remained low in all seasons (median 3·27 μg daily, range 2·76-4·15) while personal UVR exposure levels were high in spring and summer, low in autumn and negligible in winter. Mean 25(OH)D levels were highest in September [28·4 ng mL⁻¹; 28% optimal, zero deficient (<5 ng mL⁻¹)], and lowest in February (18·3 ng mL⁻¹; 7% optimal, 5% deficient). A February 25(OH)D level of 20 ng mL⁻¹ was achieved following a mean (95% confidence interval) late summer level of 30·4 (25·6-35·2) and 34·9 (27·9-41·9) ng mL⁻¹ in women and men, respectively, with 62% of variance explained by gender and September levels. Late summer 25(OH)D levels approximating the optimal range are required to retain sufficiency throughout the U.K. winter. Currently the majority of the population fails to reach this post-summer level and becomes vitamin D insufficient during the winter.


Jejunal gastrointestinal stromal tumour masquerading as an ovarian cancer: A case report.
A 60-year-old lady presented with lower abdominal discomfort and a huge palpable intra-abdominal mass for 4 months, with significant weight loss over half a year. Transvaginal ultrasonography and computed tomography (CT) abdomen showed a large right solid cystic mass likely ovarian in origin. The CA-125 was raised. With the provisional diagnosis of ovarian cancer patient underwent laparotomy at Hospital Umum Sarawak, Malaysia. However intraoperative findings showed that uterus and both ovaries were normal. The tumour was arising from the jejunum and adherent to the dome of the urinary bladder and right broad ligament. The tumour was resected and final diagnosis was jejunal gastrointestinal stromal tumour (GIST). We described this case which was misinterpreted as an ovarian cancer.


FOXP3 ensembles in T-cell regulation.
Our recent studies have identified dynamic protein ensembles containing forkhead box protein 3 (FOXP3) that provide insight into the molecular complexity of suppressor T-cell activities, and it is our goal to determine how these ensembles regulate FOXP3's transcriptional activity in vivo. In this review, we summarize our current understanding of how FOXP3 expression is induced and how FOXP3 functions in vivo as a transcriptional regulator by assembling a multisubunit complex involved in histone modification as well as chromatin remodeling.


The binding affinities of proteins interacting with the PDZ domain of PICK1.
Protein interacting with C kinase (PICK1) is well conserved throughout evolution and plays a critical role in synaptic plasticity by regulating the trafficking and posttranslational modification of its interacting proteins. PICK1 contains a single PSD95/DlgA/Zo-1 (PDZ) protein-protein interaction domain, which is promiscuous and shown to interact with over 60 proteins, most of which play roles in neuronal function. Several reports have suggested the role of PICK1 in disorders such as epilepsy, pain, brain trauma and stroke, drug abuse and dependence, schizophrenia and psychosis. Importantly, lead compounds that block PICK1 interactions are also now becoming available. Here, a new modeling approach was developed to investigate binding affinities of PDZ interactions. Using these methods, the binding affinities of all major PICK1 interacting proteins are reported and the effects of PICK1 mutations on these interactions are described. These modeling methods have important implications in defining the binding properties of proteins interacting with PICK1 as well as the general structural requirements of PDZ interactions. The study also provides modeling methods to support in the drug design of ligands for PDZ domains, which may further aid in development of the family of PDZ domains as a drug target.


Eye-Hand Coordination during Visuomotor Adaptation with Different Rotation Angles: Effects of Terminal Visual Feedback.
This study examined adaptive changes of eye-hand coordination during a visuomotor rotation task under the use of terminal visual feedback. Young adults made reaching movements to targets on a digitizer while looking at targets on a monitor where the rotated feedback (a cursor) of hand movements appeared after each movement. Three rotation angles (30°, 75° and 150°) were examined in three groups in order to vary the task difficulty. The results showed that the 30° group gradually reduced direction errors of reaching with practice and adapted well to the visuomotor rotation. The 75° group made large direction errors of reaching, and the 150° group applied a 180° reversal shift from early practice. The 75°and 150° groups, however, overcompensated the respective rotations at the end of practice. Despite these group differences in adaptive changes of reaching, all groups gradually adapted gaze directions prior to reaching from the target area to the areas related to the final positions of reaching during the course of practice. The adaptive changes of both hand and eye movements in all groups mainly reflected adjustments of movement directions based on explicit knowledge of the applied rotation acquired through practice. Only the 30° group showed small implicit adaptation in both effectors. The results suggest that by adapting gaze directions from the target to the final position of reaching based on explicit knowledge of the visuomotor rotation, the oculomotor system supports the limb-motor system to make precise preplanned adjustments of reaching directions during learning of visuomotor rotation under terminal visual feedback.


Residual social, memory and oxytocin-related changes in rats following repeated exposure to γ-hydroxybutyrate (GHB), 3,4-methylenedioxymethamphetamine (MDMA) or their combination.
There has been little investigation of the possible lasting adverse effects of γ-hydroxybutyrate (GHB). This study aims to study whether GHB produces residual adverse effects on memory and social behaviour in rats and lasting changes in brain monoamines and oxytocin-related gene expression. Rats received daily intraperitoneal injections of GHB (500 mg/kg), methylenedioxymethamphetamine (MDMA; 5 mg/kg) or their combination (GHB/MDMA) over ten consecutive days. Locomotor activity and body weight were assessed during the dosing period and withdrawal-related anxiety was assessed 24 h after drug cessation. After a washout of 4 weeks, rats were tested on the emergence, social interaction, and object recognition tasks over a 2-week period. Monoamine levels in cortex and striatum, and hypothalamic oxytocin and oxytocin receptor mRNA, were then assessed. MDMA and GHB/MDMA caused modest sensitization of locomotor activity over time, while sedative effects of GHB diminished with repeated exposure. GHB-treated rats showed reduced social interaction 24 h after the final dose, indicating GHB withdrawal-induced anxiety. All drug-treated groups displayed residual deficits in social interaction and object recognition. No changes in monoamine levels were detected 8 weeks post-drug. However, MDMA pre-exposure increased hypothalamic oxytocin mRNA while GHB pre-exposure upregulated oxytocin receptor mRNA. GHB/MDMA pre-exposure caused intermediate changes in both of these measures. GHB treatment caused residual impairments in memory and social behaviour and increases in anxiety, paralleling the lasting adverse effects of MDMA. Both drugs caused lasting neuroadaptations in brain oxytocin systems and this may be related to the long-term social interaction deficiencies caused by both drugs.


Influence of streptozitocin-induced diabetes on glycosyltransferase activities in plasma and renal cortex.
The collagen glucosyltransferase of renal cortex is increased in experimental diabetes and this increased may be partially reversed or prevented by insulin treatment. The absence of any consistent increase in the plasma collagen glucosyltransferase level in diabetes argues against the enzyme's having a significant role in the pathological thickening of capillary basement membranes. The biological significance of the increased renal glucosyltransferase activity in chemically-induced diabetes must therefore remain in doubt but it is possible that the high glucose concentration in the blood simply stimulates the synthesis of new enzyme protein in the kidney.


Sustaining the vitality of colonoscopy quality improvement programmes over time. Experience from the Norwegian Gastronet programme.
An important challenge of any quality assurance (QA) programme is to maintain interest among participants to ensure high data quality over time. The primary aim of this study was to identify factors associated with endoscopist compliance with the Norwegian QA programme for colonoscopies (Gastronet). The Gastronet registration tools are an endoscopy report form to be filled in directly after the procedure by the endoscopist, and a satisfaction questionnaire to be filled in by the patient on the day after the examination. During the study period from 1 January 2004 to 31 December 2006, endoscopist compliance was measured by assessing patient report coverage, defined as the percentage of patient satisfaction questionnaires received by the Gastronet secretariat divided by the total number of colonoscopy reports registered by the individual endoscopists during the study period. Multivariate logistic regression models were applied to identify individual factors related to patient report coverage. Eighty-eight endoscopists from 10 hospitals contributed a total of 16,149 colonoscopies. Overall patient report coverage decreased from 87% in 2004 to 80% in 2006. A low patient report coverage was associated with time since the registrations started [odds ratio (OR) 0.98, 95% confidence interval (CI) 0.97-0.98; P < 0.001], use of sedation (OR 0.7, 95% CI 0.61-0.76; P < 0.001), and incomplete colonoscopy (OR 0.6, 95% CI 0.54-0.76; P < 0.001). Decreasing compliance with registration over time may compromise data quality and the validity of the results. Lower coverage of patient's reports (presumably for the most difficult examinations) may lead to erroneous conclusions regarding colonoscopy performance.


Modular architecture of Munc13/calmodulin complexes: dual regulation by Ca2+ and possible function in short-term synaptic plasticity.
Ca(2+) signalling in neurons through calmodulin (CaM) has a prominent function in regulating synaptic vesicle trafficking, transport, and fusion. Importantly, Ca(2+)-CaM binds a conserved region in the priming proteins Munc13-1 and ubMunc13-2 and thus regulates synaptic neurotransmitter release in neurons in response to residual Ca(2+) signals. We solved the structure of Ca(2+)(4)-CaM in complex with the CaM-binding domain of Munc13-1, which features a novel 1-5-8-26 CaM-binding motif with two separated mobile structural modules, each involving a CaM domain. Photoaffinity labelling data reveal the same modular architecture in the complex with the ubMunc13-2 isoform. The N-module can be dissociated with EGTA to form the half-loaded Munc13/Ca(2+)(2)-CaM complex. The Ca(2+) regulation of these Munc13 isoforms can therefore be explained by the modular nature of the Munc13/Ca(2+)-CaM interactions, where the C-module provides a high-affinity interaction activated at nanomolar [Ca(2+)](i), whereas the N-module acts as a sensor at micromolar [Ca(2+)](i). This Ca(2+)/CaM-binding mode of Munc13 likely constitutes a key molecular correlate of the characteristic Ca(2+)-dependent modulation of short-term synaptic plasticity.


Deep Learning to Speed up the Development of Structure-Property Relations For Hexagonal Boron Nitride and Graphene.
Structure-property maps play a key role in accelerated materials discovery. The current norm for developing these maps includes computationally expensive physics-based simulations. Here, the capabilities of deep learning agents are explored such as convolutional neural networks (CNNs) and multilayer perceptrons (MLPs) to predict structure-property relations and reduce dependence on simulations. This study contains simulated hexagonal boron nitride (h-BN) microstructures damaged by various levels of radiation and temperature, with the objective to predict their residual strengths from the final atomic positions. By developing low dimensional physical descriptors to statistically describe the defects, these results show that purpose-specific microstructure representation can help in achieving a good prediction accuracy at low computational cost. Furthermore, the adaptability of the trained deep learning agents is explored to predict structure-property maps of other 2D materials using transfer learning. It is shown that in order to achieve good predictions accuracy (≈95% R2 ), an agent that is training for the first time ("learning from scratch") requires 23-45% of simulated data, whereas an agent adapting to a different material ("transfer learning") requires only about 10% or less. This suggests that transfer learning is a potential game changer in material discovery and characterization approaches.


Where's My Button? Evaluating the User Experience of Surface Haptics in Featureless Automotive User Interfaces.
Advancements in user interface technologies and demands of design engineering led to increasing implementation of large and mostly flat interactive surfaces in automotive. Recent discussions in the context of in-vehicle usage of touchscreens advocate for the use of haptic feedback to restore the explore- and feel-qualities typically experienced in traditional physical button interfaces that contribute to intuitive, eyes-free, and tactually rich interactions. Haptic technologies that include a friction modulation approach seem especially promising to convey a high-quality feeling. This research reports an experience-oriented evaluation of an electrostatic friction haptic display in an in-vehicle direct touch interaction context. The evaluation was based on an automotive multitask setting (primary driving-task and secondary target-selection-task) with a 2 × 2 feedback modality design (factors haptic/audio with levels absent/present). The objective variables (response time, errors, and performance on the primary task) did not differ between feedback modalities. Any additional feedback to a visual baseline enhanced the user experience, with the multimodal feedback being preferred by most participants. Surface haptics was perceived as a novel yet unexpected type of haptic feedback. We discuss the implications for the haptic design of programmable friction displays and provide an initial set of guidelines for this innovative technology.


Oculocutaneous tyrosinaemia or tyrosinaemia type 2: a case report.
Oculo-cutaneous tyrosinaemia type II is an autosomal recessive disease due to an abnormality of tyrosine metabolism, probably because of a deficiency of cytoplasmic tyrosine aminotransferase. It presents as a varying association of focal palmoplantar keratosis, bilateral keratitis and mental retardation. Herein, we report an 8-year-old boy with palmoplantar hyperkeratosis with peripheral oozing and dendritic keratitis appearing after the skin lesions. There was no mental deterioration despite the long delay in diagnosis of the disorder. The diagnosis was confirmed by the presence of hypertyrosinaemia and the absence of hepatorenal lesion. The child exhibited a remarkable degree of improvement in the hyperkeratotic lesions and keratitis after the dietary modifications were instituted. In conclusion, chronic focal bullous palmoplantar hyperkeratosis along with keratitis should alert the clinician to screen for abnormal serum and/or urine tyrosine level. Awareness of the presenting signs and symptoms may speed up the diagnosis and initiation of a tyrosine and phenylalanine-restricted diet that is most efficient in improving the symptoms and preventing visual and cognitive impairment.


Ocular complications of the acquired immunodeficiency syndrome.
The acquired immunodeficiency syndrome (AIDS) affects the ocular structures in several ways. Kaposi's sarcoma has been observed on the bulbar conjunctiva of the globe. Retinal complications, however, are of major concern. Cotton-wool spots are commonly seen in AIDS patients and are usually of no consequence, except that they must be distinguished from the early stages of cytomegalovirus (CMV) retinitis, seen in 20-40% of these patients. CMV causes a necrotic-type retinitis potentially leading to blindness. 9-[2-Hydroxy-1-(hydroxymethyl)ethoxymethyl]guanine (DHPG) has been found effective in the short-term treatment of this disorder. It is planned to use AS101 in the regimen to see if a long-term cure from this disease can be affected. Care must be taken in handling ocular tissue of AIDS patients or the re-use of ophthalmic instruments touching the eye of AIDS patients since the human immunodeficiency virus has been found in these structures.


Predictors of bacterial meningitis in resource-limited contexts: an Angolan case.
Despite the great morbidity and mortality that childhood bacterial meningitis (BM) is experiencing in Africa, diagnosis of BM in resource-limited contexts is still a challenge. Several algorithms and clinical predictors have been proposed to help physicians in decision-making but a lot of these markers used variables that are calculable only in well-equipped laboratories. Predictors or algorithm based on parameters that can be easily performed in basic laboratories can help significantly in BM diagnosis, even in resource-limited settings, rural hospitals or health centers. This retrospective study examined 145 cerebral-spinal fluid (CSF) specimens from children from 2 months to 14 years. CSF specimens were divided into two groups, according to the presence or not of a clinical diagnosis of BM. For each specimen, CSF aspect, CSF white blood cells (WBC) count, CSF glucose and protein concentration were analyzed and statistical analysis were performed. CSF WBC count ≥10/µl is no more a valuable predictor of BM. CSF protein concentration ≥50 mg/dl has a better sensitivity for BM diagnosis and when used with CSF glucose concentration ≤40 mg/dl, can help to diagnose correctly almost all the BM cases. An algorithm including CSF protein concentration, glucose concentration and WBC count has been proposed to rule out BM and to correctly diagnose it. In resource-limited health centers, the availability of a combination of easy-to-obtain parameters can significantly help physicians in BM diagnosis. The prompt identification of a BM case can be rapid treated or transferred to adequate structures and can modify the outcome in the patient.


Kinetics and mechanism of the oxidation of N-acetyl homocysteine thiolactone with aqueous iodine and iodate.
The kinetics of N-acetyl homocysteine thiolactone (NAHT) oxidation by aqueous iodine and iodate were studied by spectrophotometric techniques. The iodate-NAHT reaction is slow and results in the formation of N-acetyl homocysteine thiolactone sulfoxide as the sole product (NAHTSO). The stoichiometry of the reaction was deduced as: IO3(-) + 3NAHT → I(-) + 3NAHTSO (S1). In excess iodate conditions, the iodide produced in S1 is oxidized to give iodine: IO3(-) + 5I(-) + 6H(+) → 3I2 + 3H2O (S2). Thus in excess iodate conditions the overall stoichiometry of the reaction is a linear combination of S1 and S2 that eliminates iodide, 5S1 + S2: 2IO3(-)+ 5NAHT+ 2H(+) → I2 + 5NAHTSO + H2O. There was a 1:1 stoichiometry for the NAHT - I2 reaction: NAHT+ I2 + H2O → NAHTSO +2I(-) + 2H(+) (S3). All reactions, S1, S2 and S3 occur simultaneously and since they are all comparable in rate; complex dynamics were observed. Iodide catalyzes S1 and S2 but inhibits S3. Iodide is a product of both S1 and S3. It has the most profound effect on the overall global dynamics observed. The overall reaction scheme which involved S1, S2 and S3 was modeled by a simple 12-reaction mechanistic scheme which gave a very good fit to experimental data.


Exact phase boundary of an amphiphile-rich phase in a ternary solution on a Bethe lattice.
A model ternary solution is considered in which the bonds of a three-coordinate Bethe lattice are covered by rodlike molecules of types AA, BB, and AB, the AB-type molecule representing an amphiphile. The phase boundary in temperature-composition space of an ordered amphiphile-rich phase is calculated exactly.


Mouse T cell membrane proteins Rt6-1 and Rt6-2 are arginine/protein mono(ADPribosyl)transferases and share secondary structure motifs with ADP-ribosylating bacterial toxins.
Mono ADP-ribosylation is a posttranslational protein modification that has been implicated in the regulation of key biological functions in bacteria as well as in animals. Recently, the first cDNAs for eucaryotic mono(ADPribosyl)transferases were cloned and found to exhibit significant sequence similarity only to one other known protein, the T cell differentiation antigen Rt6. In this paper we describe secondary structure analyses of Rt6 and related proteins and show conserved structure motifs and amino acid residues consistent with a common ancestry of these eucaryotic proteins and bacterial ADP-ribosyltransferases. Moreover, we have expressed soluble mouse Rt6-1 and Rt6-2 gene products in which C-terminal tags (FLAG-His6) replace the native glycosylphosphatidylinositol anchor signal sequences. Purified recombinant Rt6-2, but not Rt6-1, shows NAD+ glycohydrolase activity, which is inhibited by the arginine analogue agmatine. Immunoprecipitation of recombinant Rt6-1 and Rt6-2 with anti-FLAG M2 antibody followed by incubation with [32P]NAD+ leads to rapid and covalent incorporation of radioactivity into the light chain of the M2 antibody. The bound label is resistant to treatment with HgCl2 but sensitive to NH2OH, characteristic of arginine-linked ADP-ribosylation. These results demonstrate that Rt6-1 and RT6-2 possess the enzymatic activities typical for NAD+-dependent arginine/protein mono(ADPribosyl)transferases (EC 220.127.116.11). They are the first such enzymes to be molecularly characterized in the immune system.


The Poggendorff illusion effect influenced by top-down control: evidence from an event-related brain potential study.
Event-related brain potentials were used to examine the neural correlates of the visual illusion effect in the Poggendorff illusion. In this study, there were three tasks, namely, illusion task 1, illusion task 2 (similar to the classical Poggendorff figures, where the two oblique lines in which individuals were prone to judge to be collinear, were not collinear in fact), and baseline task. Scalp event-related brain potential analysis revealed that (a) both illusion task 1 and illusion task 2 elicited a more negative event-related brain potential deflection (N400-600) than did baseline task, approximately 400 ms after onset of the stimuli, and (b) high-level cognitive control system is, through enhancing the influence of the context on identifying the relationships of the two oblique lines, involved in generating the Poggendorff illusion.


The origins and overview of the W. K. Kellogg Community Health Scholars Program.
This paper describes the history and components of the W. K. Kellogg Community Health Scholars Program (CHSP). From 1998 to 2007, CHSP trained 46 postdoctoral fellows to develop and enhance skills in working with communities and engage in community-based participatory research (CBPR). The original goal of CHSP was to increase the number of faculty at health professional schools who possess the capacity to carry out CBPR and teaching; however, the goal of the program was revised to highlight the importance of having public health professionals in all professional settings with CBPR knowledge and expertise. CHSP was a training program whose design and implementation exemplified the partnership principles at the core of the training it provided. An external participatory evaluation was conducted to strengthen the maturing program. Key program components included a National Advisory Committee, training sites, academic and community mentorship, and a structured Scholar Program Plan. The CHSP has had an impact on academic institutions, community-based organizations (CBOs), policies relating to research funding and implementation, and professional organizations (e.g., founded the Community-Based Public Health Caucus of the American Public Health Association). As the result of the continued interaction of CHSP alumni and their academic and community mentors and partners, that which began as a training program evolved into much more. Although the CHSP as a discrete program came to an end in 2007, its principles and methods were sustained as it continued as the Community Track of the Kellogg Health Scholars Program in that year.


Missing canines: a novel aetiology.
Infant oral mutilation is the practice of removing developing tooth germs, commonly the mandibular canine, in infants up to the age of 1 year. Subsequent complications include missing, impacted or hypoplastic permanent anterior and canine teeth. We report on a case of bilaterally missing lower canines thought to be due to infant oral mutilation. It is important that general dental practitioners are aware of this practice and resulting complications when treating families from sub-Saharan East Africa.


[Identification of grades division to diminished criminal responsibility in mental disorder offender].
To explore the basis to discriminate diminished criminal responsibility. Chi-square test, one-way ANOVA test, factor analysis and stepwise discriminant analyses were conducted for 92 cases which were divided into three groups according to the degree of diminished criminal responsibility. There were significant differences in the type of crime and rating score among three groups. The factor 1 reflecting the premeditation and preparation before crime was the most important of all factors. Realistic motivation, time selectivity of offending, emotion during the crime, understanding the nature of the behavioral, impairment of life ability and impairment of reality testing were the discriminating factors of grades division in diminished criminal responsibility. The diminished criminal responsibility in mental disorder offender could be divided into three grades.


Breast reconstruction utilizing implants: a local experience and comparison of three techniques.
The breast reconstruction patient requires accurate information about the complications, failures, and additional surgeries associated with implant reconstruction. In this series of consecutive patients, we examine three methods of implant reconstruction: (1) immediate with a permanent implant/expander (86 patients/107 breasts), (2) delayed with a permanent implant/expander (57/73), and (3) delayed serial expansion with gel/saline (54/68). Implant/expander reconstructions had an equal interval to completion (immediate 118 days, delayed 127 days), a significant need for revisions (immediate 57 percent, delayed 30 percent), and a similar complication rate (10 percent) and failure rate (3.5 percent). The delayed serial expansion patients were completed with one operation 66 percent of the time, and only 9 percent required revisional surgery. The data obtained from the largest private health care provider in the state confirmed a significant difference (p = 0.003) in the need for revisional surgery between immediate and delayed reconstructions. The data showed immediate implant reconstructions to (1) be safe (low failure rate), (2) require more capsular intervention procedures, (3) have a greater expense, and (4) have good aesthetic results (90 percent Baker class I or II) because of revisional surgery. The immediate implant breast reconstruction patients are committed to their reconstruction and undergo revisional surgery to improve their aesthetic result. Delayed implant reconstruction patients are less likely to undergo further surgery to correct capsular deformities.


Thermometric lateral flow immunoassay with colored latex beads as reporters for COVID-19 testing.
Temperature sensing is a promising method of enhancing the detection sensitivity of lateral flow immunoassay (LFIA) for point-of-care testing. A temperature increase of more than 100 °C can be readily achieved by photoexcitation of reporters like gold nanoparticles (GNPs) or colored latex beads (CLBs) on LFIA strips with a laser power below 100 mW. Despite its promise, processes involved in the photothermal detection have not yet been well-characterized. Here, we provide a fundamental understanding of this thermometric assay using non-fluorescent CLBs as the reporters deposited on nitrocellulose membrane. From a measurement for the dependence of temperature rises on the number density of membrane-bound CLBs, we found a 1.3-fold (and 3.2-fold) enhancement of the light absorption by red (and black) latex beads at 520 nm. The enhancement was attributed to the multiple scattering of light in this highly porous medium, a mechanism that could make a significant impact on the sensitivity improvement of LFIA. The limit of detection was measured to be 1 × 105 particles/mm2. In line with previous studies using GNPs as the reporters, the CLB-based thermometric assay provides a 10× higher sensitivity than color visualization. We demonstrated a practical use of this thermometric immunoassay with rapid antigen tests for COVID-19.


Hepatocellular carcinoma with gastrointestinal hemorrhage caused by direct tumor invasion to the duodenum.
Gastrointestinal hemorrhage from hepatocellular carcinoma invading the duodenum is very rare. A 60-year-old man with multiple hepatocellular carcinoma was admitted to our hospital because of massive melena and hematemesis. We succeeded in hemostasis of an esophageal variceal rupture by endoscopic varicial ligation. The duodenum could not be observed endoscopically due to extramural compression to the stomach from the liver tumor. Massive gastrointestinal hemorrhage occurred again and the patient died of hepatic failure. The postmortem examination revealed that the liver tumor had invaded the second portion of the duodenum and perforated into the lumen.


An Unusual Polypoid Septal Mucosal Melanoma: Overview and Diagnostic Pitfalls.
Sinonasal mucosa is an area of high melanocyte density compared to other mucosa-lined sites. Sinonasal mucosal melanomas (SNMM) most commonly arise from the nasal cavity and the paranasal sinuses. Due to their obscure anatomic location and lack of early symptomatology, SNMM are often diagnosed in an advanced stage. The majority of patients who present with symptoms complain of unilateral nasal dysfunction, such as obstruction and epistaxis. We hereby report a case of an 86-year-old female, who presented with a three-year history of progressive right-sided nasal obstruction and recurrent epistaxis. Posterior rhinoscopy and endoscopy revealed a polypoid, fleshy lesion whose coloration varied from mildly pigmented to amelanotic. Inverted sinonasal papilloma was included in the differential diagnosis due to MRI findings. Post-resection histopathology indicated a mucosal melanoma. Typically, amelanotic lesions are rare, more difficult to diagnose and associated with worse prognosis due to both their aggressiveness and delayed diagnosis.


Centrosomal PKCbetaII and pericentrin are critical for human prostate cancer growth and angiogenesis.
Angiogenesis is critical in the progression of prostate cancer. However, the interplay between the proliferation kinetics of tumor endothelial cells (angiogenesis) and tumor cells has not been investigated. Also, protein kinase C (PKC) regulates various aspects of tumor cell growth, but its role in prostate cancer has not been investigated in detail. Here, we found that the proliferation rates of endothelial and tumor cells oscillate asynchronously during the growth of human prostate cancer xenografts. Furthermore, our analyses suggest that PKCbetaII was activated during increased angiogenesis and that PKCbetaII plays a key role in the proliferation of endothelial cells and tumor cells in human prostate cancer; treatment with a PKCbetaII-selective inhibitor, betaIIV5-3, reduced angiogenesis and tumor cell proliferation. We also find a unique effect of PKCbetaII inhibition on normalizing pericentrin (a protein regulating cytokinesis), especially in endothelial cells as well as in tumor cells. PKCbetaII inhibition reduced the level and mislocalization of pericentrin and normalized microtubule organization in the tumor endothelial cells. Although pericentrin has been known to be up-regulated in epithelial cells of prostate cancers, its level in tumor endothelium has not been studied in detail. We found that pericentrin is up-regulated in human tumor endothelium compared with endothelium adjacent to normal glands in tissues from prostate cancer patients. Our results suggest that a PKCbetaII inhibitor such as betaIIV5-3 may be used to reduce prostate cancer growth by targeting both angiogenesis and tumor cell growth.


VHL Germline Mutations in Argentinian Patients with Clinical Diagnoses or Single Typical Manifestations of Type 1 von Hippel-Lindau Disease.
von Hippel-Lindau (VHL) disease is caused by mutations in the VHL tumor suppressor gene. As tumors that develop in the context of VHL also occur in a sporadic context, the frequency of this syndrome may be underestimated. Our aim was to identify VHL gene mutations in Argentinian patients who fulfilled the clinical criteria for type 1 VHL disease and in patients with VHL-associated manifestations that did not meet these criteria. We performed a retrospective cohort study, including patients who met current diagnostic criteria for type 1 VHL (Group 1, n = 19) and patients with VHL-associated manifestations that did not meet these criteria (Group 2, n = 21). Genomic DNA was extracted from peripheral blood leukocytes. Mutation analysis involved DNA sequencing, while large deletions were determined by universal primer quantitative fluorescent multiplex polymerase chain reaction (UPQFM-PCR) and multiplex ligation-dependent probe amplification (MLPA) analysis. VHL mutations were detected in 16/19 (84.2%) patients in Group 1 and included: gross deletions (4/16); nonsense mutations (6/16); frameshift mutations (4/16); missense mutations (1/16); and splicing mutations (1/16). Three of these mutations were novel. No alterations were found in 3 of 19 VHL patients. In Group 2, one nonsense VHL mutation was detected in a young patient with a solitary central nervous system hemangioblastoma without familial history. A study of 30 first-degree relatives revealed four carriers with VHL mutations. We found three novel mutations in the VHL gene in our population. Our results emphasize the importance of a complete genetic study of VHL to confirm type 1 VHL disease, not only in patients with clinical diagnostic criteria but also in those presenting a single typical manifestation.


Assessing the accuracy of protein structures by quantum mechanical computations of 13C(alpha) chemical shifts.
Two major techniques have been used to determine the three-dimensional structures of proteins: X-ray diffraction and NMR spectroscopy. In particular, the validation of NMR-derived protein structures is one of the most challenging problems in NMR spectroscopy. Therefore, researchers have proposed a plethora of methods to determine the accuracy and reliability of protein structures. Despite these proposals, there is a growing need for more sophisticated, physics-based structure validation methods. This approach will enable us to (a) characterize the "quality" of the NMR-derived ensemble as a whole by a single parameter, (b) unambiguously identify flaws in the sequence at a residue level, and (c) provide precise information, such as sets of backbone and side-chain torsional angles, that we can use to detect local flaws. Rather than reviewing all of the existing validation methods, this Account describes the contributions of our research group toward a solution of the long-standing problem of both global and local structure validation of NMR-derived protein structures. We emphasize a recently introduced physics-based methodology that makes use of observed and computed (13)C(alpha) chemical shifts (at the density functional theory (DFT) level of theory) for an accurate validation of protein structures in solution and in crystals. By assessing the ability of computed (13)C(alpha) chemical shifts to reproduce observed (13)C(alpha) chemical shifts of a single structure or ensemble of structures in solution and in crystals, we accomplish a global validation by using the conformationally averaged root-mean-square deviation, ca-rmsd, as a scoring function. In addition, the method enables us to provide local validation by identifying a set of individual amino acid conformations for which the computed and observed (13)C(alpha) chemical shifts do not agree within a certain error range and may represent a nonreliable fold of the protein model. Although it is computationally intensive, our validation method has several advantages, which we illustrate through a series of applications. This method makes use of the (13)C(alpha) chemical shifts, not shielding, that are ubiquitous to proteins and can be computed precisely from the phi, psi, and chi torsional angles. There is no need for a priori knowledge of the oligomeric state of the protein, and no knowledge-based information or additional NMR data are required. The primary limitation at this point is the computational cost of such calculations. However, we anticipate that enhancements in the speed of calculating these chemical shifts coupled with the ever-increasing computational power should soon make this a standard method accessible to the general NMR community.


Dry but Not Humid Thermal Processing of Aloe vera Gel Promotes Cytotoxicity on Human Intestinal Cells HT-29.
Aloe vera products, both in food and cosmetics, are becoming increasingly popular due to their claimed beneficial effects, which are mainly attributed to the active compound acemannan. Usually, these end products are based on powdered starting materials. High temperatures during the drying process to obtain the starting materials have several advantages, like shortening the drying time, eliminating toxic aloin and reducing bacterial contamination. Nevertheless, there are two major drawbacks: first, at temperatures of 80 °C or higher, structural changes in acemannan, especially its deacetylation (>46%), are triggered, which does not happen at lower temperatures (14% at 60 °C); secondly, a toxic principle is formed at higher temperatures, resulting in a higher cytotoxicity. Thus, two temperature-dependent but opposing effects cause with a median cytotoxic concentration of CC50 = 0.4× a peak of cytotoxicity at 80 °C; at 60 °C this cytotoxic substance is not formed and at 100 °C aloin is more readily eliminated, resulting in a CC50 = 1.1× and CC50 = 1.4×, respectively. The cytotoxic substance generated by dry heat at 80 °C is not a modified polysaccharide because its polysaccharide-enriched alcohol-insoluble fraction is with CC50 = 0.9× less cytotoxic. Moreover, this substance is polar enough to be washed away with ethanol. Additionally, when Aloe gel is heated at 80 °C under humid conditions (pasteurization), the cytotoxicity does not increase (CC50 = 1.6×). Finally, to produce powdered starting materials from Aloe gel, it is recommended to use temperatures of around 60 °C in order to preserve the acemannan structure (and thus biological activity) and the low cytotoxicity.


A Not So Perfect Score: Factors Associated with the Rate of Straight Line Scoring in Oncology Training Programs.
Straight line scoring (SLS), defined as trainee assessments with the same score for all evaluation items, is statistically improbable and potentially indicates inaccurate assessment. Factors contributing to higher SLS rates are unknown, and knowledge of SLS prevalence within oncologic training is lacking. SLS frequency was measured for evaluations from all Accreditation Council for Graduate Medical Education (ACGME)-accredited programs at a single cancer care institution between 2014 and 2018. SLS prevalence was estimated using hierarchical linear models (HLM) that considered characteristics of evaluator, trainee, and evaluation potentially related to SLS. Results were compared with national SLS rates. Six thousand one hundred sixty evaluations were included from 476 evaluators. Overall prevalence of SLS was 12.1% (95% CI 4.5-28.8). Residents (vs fellows) were less likely to have SLS evaluations (OR 0.5, 95% CI 0.4-0.8), though for all trainees increasing training year corresponded with increasing SLS frequency (OR 1.5, 95% CI 1.3-1.7). SLS was more common in procedural specialties compared with medical specialties (OR 2.1, 95% CI 1.1-3.8). Formative evaluations had lower SLS rates (OR 0.6, 95% CI 0.5-0.9) than summative evaluations, while milestone-based evaluations had higher rates than those that were not milestone-based (OR 1.5, 95% CI 1.03-2.2). Features of evaluators, such as subspecialty within oncology, and of trainees, such as seniority or trainee type, were related to SLS. Summative intent and milestone-based evaluations were more likely to be straight line scored. Specific evaluation scenarios at higher risk of SLS should be further examined.


The precautionary principle and the regulation of U.S. food and drug safety.
This article probes the advisability of regulating U.S. food and drug safety according to the precautionary principle. To do so, a precautionary regulatory regime is formulated on the basis of the beliefs that motivate most proponents of this initiative. That hypothetical regime is critically analyzed on the basis of an actual instantiation of a similarly stylized initiative. It will be argued that the precautionary principle entails regulatory constraints that are apt to violate basis tenets of political legitimacy. The modifications that would change this finding would also change precautionary regulation to the point that it would be indistinguishable from orthodox safety protocols. It is concluded on the basis of its impoverished content that the precautionary principle should not be taken seriously as a formal approach to the regulation of U.S. food and drug safety.


[A case of locally advanced gastric cancer responding to preoperative S-1/CDDP combination chemotherapy].
A 59-year-old man visited our department with the complaint of an abdominal mass. After detailed examination, he was diagnosed with cT3 (SE) N2M0, cStage III C gastric cancer and underwent a 3 course preoperative S-1/CDDP combination chemotherapy. After tumor down-staging was achieved after the 3 course combination chemotherapy, a surgery was scheduled. The patient underwent distal gastrectomy with D2 lymph node dissection. Histopathological diagnosis was M, type 1, 75 × 35 mm, papillary>moderately-differentiated tubular adenocarcinoma [pT2 (MP), ly3, v0, pN2, Stage IIB]. The patient is now treated with oral S-1 as postoperative adjuvant chemotherapy on an outpatient basis, and there are no signs of recurrence as of 1 year after the surgery. Preoperative chemotherapy appears to be a promising treatment option for gastric cancer with extensive lymph node metastasis.


Photodynamic therapy (PDT) in Barrett's esophagus with dysplasia or early cancer.
Esophagectomy is the standard treatment for high-grade dysplasia (HGD) and intramucosal adenocarcinoma (IMC) arising within Barrett's esophagus. Results of photodynamic therapy (PDT) were retrospectively studied to evaluate the effectiveness of PDT in ablating HGD and/or IMC complicating Barrett's esophagus. Thirty-one patients unfit for or refusing esophagectomy (male: 20, mean age: 73.4+/-9.3 years) underwent Porfimer sodium PDT ablation of their HGD (15 patients), HGD plus IMC (10 patients) or submucosal/limited T2 adenocarcinoma (6 patients). The mean Barrett's length was 5.8+/-2.2 cm. Pre-PDT endoscopic mucosal resection or Nd:YAG laser ablation of mucosal nodularity within Barrett's segment was offered in six patients. The main PDT complications were esophagitis (16.1%), photoreactions (12.9%) and stricture requiring dilatation (6.25%). The median post-PDT follow-up was 14 months. The long-term results were (a) for HGD/IMC: initial complete response (endoscopic and histologic absence of HGD-IMC) to PDT was observed in 80.95% of patients, partial response (no endoscopic abnormality, residual IMC-HGD on biopsy) in 9.52%, no response in 9.52% (the recurrence rate after an initial complete response was 17.64%) and (b) for T1b/limited T2 tumors: two patients died from cancer after 24 and 46 months, no evidence of tumor was found in two patients after 12 and 19 months and tumor recurrence was seen in two after 15 and 17 months. The mean survival was 22.1+/-12.3 months. PDT is effective in ablating HGD/IMC complicating Barrett's esophagus in the majority of cases, while it also seems to be quite effective in treating T1b/limited T2 carcinomas.


Y-931, a novel atypical antipsychotic drug, is less sensitive to oxidative phenomena.
The oxidation behavior of Y-931, a potent atypical antipsychotic drug, was compared with that of clozapine and olanzapine. In two enzymatic systems (horseradish peroxidase (HRP)/glutathione (GSH) and HRP/H(2)O(2)/GSH) which generate thiyl radicals, clozapine markedly strengthened the electron paramagnetic resonance (EPR) signal for the radical. Olanzapine, Y-931 and the major metabolites (compounds 1-3) had no or minimal effect on the intensity of this signal. In addition, the redox potential values for the three derivatives were in accord with the EPR spin trapping results. In toxicological experiments in human leukocytes, a concentration-dependent toxicity was observed when neutrophils were incubated with clozapine (1-10 micromol/l) and H(2)O(2) (1 mmol/l). However, Y-931 and olanzapine did not show remarkable toxicity under the conditions.


Investigations of protons passing through the CR-39/PM-355 type of solid state nuclear track detectors.
Solid State Nuclear Track Detectors of the CR-39∕PM-355 type were irradiated with protons with energies in the range from 0.2 to 8.5 MeV. Their intensities and energies were controlled by a Si surface barrier detector located in an accelerator scattering chamber. The ranges of protons with energies of 6-7 MeV were comparable to the thickness of the PM-355 track detectors. Latent tracks in the polymeric detectors were chemically etched under standard conditions to develop the tracks. Standard optical microscope and scanning electron microscopy techniques were used for surface morphology characterization.


Characterization of synthetic polymers by electrospray-assisted pyrolysis ionization-mass spectrometry.
Rapid characterization of synthetic polymers based on the differences in the appearance of the polar pyrolysate ions was achieved by electrospray-assisted pyrolysis ionization-mass spectrometry. The pyrolytical products produced by a commercial Curie point pyroprobe were conducted to the tip of a capillary, where charged methanol droplets were generated continuously by electrospray. Polar components in the pyrolysates may react directly with the protonated methanol ions or fuse with the charged methanol droplets; electrospray ionization proceeds from the fused droplets to generate protonated analyte ions. The mass spectra obtained through this approach were used to rapidly distinguish the polymer standards that differ in the nature of building units, degrees of polymerization, and copolymerization coefficients.


Distribution of interneurons in the CA2 region of the rat hippocampus.
The CA2 region of the mammalian hippocampus is a unique region with its own distinctive properties, inputs and pathologies. Disruption of inhibitory circuits in this region appears to be linked with the pathology of specific psychiatric disorders, promoting interest in its local circuitry, its role in hippocampal function and its dysfunction in disease. In previous studies, CA2 interneurons, including a novel subclass of CA2 dendrite-preferring interneurons that has not been identified in other CA regions, have been shown to display physiological, synaptic and morphological properties unique to this sub-field and may therefore play a crucial role in the hippocampal circuitry. The distributions of immuno-labeled interneurons in dorsal CA2 were studied and compared with those of interneurons in CA1 and CA3. Like those in CA1 and CA3, the somata of CA2 parvalbumin-immunoperoxidase-labeled interneurons were located primarily in Stratum Pyramidale (SP) and Stratum Oriens (SO), with very few cells in Stratum Radiatum (SR) and none in Stratum Lacunosum Moleculare (SLM). There was, however, a greater proportion of GAD-positive cells were immunopositive for PV in SP in CA2 than in CA1 or CA3. CA2 SP also contained a larger density of somatostatin-, calbindin-, and VIP-immunopositive somata than CA1 and/or CA3. Like those in CA1 and CA3, CCK-immunopositive somata in CA2 were mostly located in SR. Reelin- and NPY- immunolabeled cell bodies were located in all layers of the three CA regions. However, a higher density of Reelin-positive somata was found in SP and SR of CA2 than in CA1 or CA3.


Detection of carcinoma in serous effusions: a review.
A malignant serous effusion is one of the most common complications of advanced tumors, indicating a poor prognosis and having a profound impact on diagnosis, treatment, and prognosis. It is of great significance to identify benign and malignant effusions quickly and accurately. Both cellular and non-cellular components in the effusion can be employed for detection, diagnostic methods are necessary to obtain a definite diagnosis and more relevant information such as tumor classification. In this review, we focus on the comparison of several widespread cytological preparation methods, enrichment technology of exfoliated cells, and present tests for serous effusions, mainly including routine and special stains, immunocytochemistry, electron microscopy, enzyme-linked immunosorbent assay, flow cytometry, and molecular analysis.


Highly Sensitive Flexible Magnetic Sensor Based on Anisotropic Magnetoresistance Effect.
A highly sensitive flexible magnetic sensor based on the anisotropic magnetoresistance effect is fabricated. A limit of detection of 150 nT is observed and excellent deformation stability is achieved after wrapping of the flexible sensor, with bending radii down to 5 mm. The flexible AMR sensor is used to read a magnetic pattern with a thickness of 10 μm that is formed by ferrite magnetic inks.


Perlecan and vascular endothelial growth factor-encoding DNA-loaded chitosan scaffolds promote angiogenesis and wound healing.
The repair of dermal wounds, particularly in the diabetic population, poses a significant healthcare burden. The impaired wound healing of diabetic wounds is attributed to low levels of endogenous growth factors, including vascular endothelial growth factor (VEGF), that normally stimulate multiple phases of wound healing. In this study, chitosan scaffolds were prepared via freeze drying and loaded with plasmid DNA encoding perlecan domain I and VEGF189 and analyzed in vivo for their ability to promote dermal wound healing. The plasmid DNA encoding perlecan domain I and VEGF189 loaded scaffolds promoted dermal wound healing in normal and diabetic rats. This treatment resulted in an increase in the number of blood vessels and sub-epithelial connective tissue matrix components within the wound beds compared to wounds treated with chitosan scaffolds containing control DNA or wounded controls. These results suggest that chitosan scaffolds containing plasmid DNA encoding VEGF189 and perlecan domain I have the potential to induce angiogenesis and wound healing.


Production of human and murine interleukin-2 by toxic shock syndrome toxin-1.
Toxic shock syndrome toxin-1 (TSST-1), isolated from Staphylococcus aureus strains associated with toxic shock syndrome (TSS), is known as a potent mitogen and interleukin-1 inducer. The potential of TSST-1 as an interleukin-2 (IL-2) inducer was tested on human peripheral blood lymphocytes (HPBL) and murine spleen lymphocytes (MSL). These cells were incubated with TSST-1 and the supernatants analysed for IL-2 production. Preincubation of IL-2-dependent indicator cells (IC) with a monoclonal antibody specific for murine IL-2 receptors inhibited their proliferation by supernatants of TSST-1-treated MSL, thus strongly suggesting that they contain IL-2. The concentrations of TSST-1 required for HPBL or MSL to produce IL-2 ranged between 10(-1) and 10(-4) micrograms/ml. The amount of IL-2 units/ml varied little from one experiment to another. In contrast, IL-2 production by PHA-stimulated HPBL or Con A-stimulated MSL showed great variability and dependence on mitogen concentration. T-cell depleted MSL exposed to TSST-1 produced less IL-2. Experiments with germ-free mice and TSST-1-primed mice demonstrated that IL-2 production is not related to TSST-1 antigenicity.


Total hip arthroplasty: comparison of two-incision and standard techniques at an AOA-accredited community hospital.
The two-incision approach to total hip arthroplasty (THA) has received increasing attention in recent years. However, the benefits of this procedure have been debated. To evaluate the two-incision THA technique compared to the standard anterolateral THA approach in a community hospital setting. A retrospective review of records from patients who had THA at Memorial Hospital of York in Pennsylvania. Outcomes for patients who received the two-incision THA technique were compared to those who had a standard anterolateral THA approach. Perioperative parameters included operation duration and complication rates. Early function was evaluated by hospital length of stay and whether patients were discharged home or to a rehabilitation center. Twenty-eight patients had 30 THAs with a two-incision technique, and 30 patients had a standard anterolateral THA. Demographic parameters were similar among both groups. The two-incision THA group had a longer mean operation time by 34 minutes but shorter hospital stay by 0.8 days. Patients in the two-incision THA group were discharged to home 87% of the time compared to 43% in the anterolateral group. In addition, 4 patients (13%) in the two-incision group had an orthopedic complication compared to no complications in the anterolateral group. There were longer operative times, shorter hospital stays, and higher complication rates among patients who received the two-incision THA. Patients who receive the two-incision THA should be selected carefully and advised about the potential for increased complications.


Effects of HOE 140 on some renal functions in type I diabetic mice.
To investigate in mice the mechanisms underlying renal functions in a type I diabetes model, we have suppressed B2 kinin receptors local activities by their specific antagonist D-Arg [Hyp3-Thi5-D-Tic7-Oic8]BK (HOE 140). Mice made diabetic with low consecutive doses of streptozotocin (STZ) (45 mg/k BW during 5 days) were injected with HOE 140 (15 micrograms/twice a day) for 15 days. This drug did not modify glycemia of STZ treated animals but a significantly reduction of urinary proteins, nitrites and kallikrein was observed. These results indicate that kinin B2-receptors activation is implicated in the alterations of renal function in this model of type I diabetes in mice.


The influence of pore size and stiffness on tenocyte bioactivity and transcriptomic stability in collagen-GAG scaffolds.
Orthopedic injuries, particularly those involving tendons and ligaments, are some of the most commonly treated musculoskeletal ailments, but are associated with high costs and poor outcomes. A significant barrier in the design of biomaterials for tendon tissue engineering is the rapid de-differentiation observed for primary tenocytes once removed from the tendon body. Herein, we evaluate the use of an anisotropic collagen-glycosaminoglycan (CG) scaffold as a tendon regeneration platform. We report the effects of structural properties of the scaffold (pore size, collagen fiber crosslinking density) on resultant tenocyte bioactivity, viability, and gene expression. In doing so we address a standing hypothesis that scaffold anisotropy and strut flexural rigidity (stiffness) co-regulate long-term maintenance of a tenocyte phenotype. We report changes in equine tenocyte specific gene expression profiles and bioactivity across a homologous series of anisotropic collagen scaffolds with defined changes in pore size and crosslinking density. Anisotropic scaffolds with higher crosslinking densities and smaller pore sizes were more able to resist cell-mediated contraction forces, promote increased tenocyte metabolic activity, and maintain and increase expression of tenogenic gene expression profiles. These results suggest that control over scaffold strut flexural rigidity via crosslinking and porosity provides an ideal framework to resolve structure-function maps relating the influence of scaffold anisotropy, stiffness, and nutrient biotransport on tenocyte-mediated scaffold remodeling and long-term phenotype maintenance.