Antiprotons created by laser ionization of antihydrogen are observed to rapidly escape the ALPHA trap. Further, positron plasmas heat more quickly after the trap is illuminated by laser light for ...several hours. These phenomena can be caused by patch potentials-variations in the electrical potential along metal surfaces. A simple model of the effects of patch potentials explains the particle loss, and an experimental technique using trapped electrons is developed for measuring the electric field produced by the patch potentials. The model is validated by controlled experiments and simulations.
Summary
Background Questionnaires are widely used in epidemiological studies to measure eczema symptom prevalence, but there are concerns regarding their accuracy if used as a diagnostic tool.
...Objectives To compare the performance of a validated eczema symptom questionnaire and a standardized skin examination protocol employed in the second phase of the International Study of Asthma and Allergies in Childhood (ISAAC).
Methods A total of 30 358 schoolchildren aged 8–12 years from 18 countries were examined for flexural eczema. Parents also completed an eczema symptom questionnaire. We compared prevalence estimates at the population level based on the questionnaire vs. physical examination. We also compared the skin examination and the ISAAC questionnaire in making a diagnosis of flexural eczema.
Results The point prevalences for flexural eczema at centre level based on a single examination were lower than the questionnaire‐based 12‐month period prevalences (mean centre prevalence 3·9% vs. 9·4%). Correlation between prevalences of both outcome measures was high (r = 0·77, P < 0·001). At the individual level, questionnaire‐derived symptoms of ‘persistent flexural eczema in the past 12 months’ missed < 10% of cases of flexural eczema detected on physical examination. However, between 33% and 100% of questionnaire‐based symptoms of ‘persistent flexural eczema in the past 12 months’ were not confirmed on examination.
Conclusions ISAAC questionnaire‐derived symptom prevalences are sufficiently precise for comparisons between populations. Where diagnostic precision at the individual level is important, questionnaires should be validated and potentially modified in those populations beforehand, or a standardized skin examination protocol should be used.
To determine the effect of radiotherapy dose on prostate cancer patient outcome and biopsy positivity in a phase III trial.
A total of 305 stage T1 through T3 patients were randomized to receive 70 ...Gy or 78 Gy of external-beam radiotherapy between 1993 and 1998. Of these, 301 were assessable; stratification was based on pretreatment prostate-specific antigen level (PSA). Dose was prescribed to the isocenter at 2 Gy per fraction. All patients underwent planning pelvic computed tomography scan to confirm prostate position. Treatment failure was defined as an increasing PSA on three consecutive follow-up visits or the initiation of salvage treatment. Median follow-up was 40 months.
One hundred fifty patients were randomized to the 70-Gy arm and 151 to the 78-Gy arm. The difference in freedom from biochemical and/or disease failure (FFF) rates of 69% and 79% for the 70-Gy and 78-Gy groups, respectively, at 5 years was marginally significant (log-rank P: =.058). Multiple-covariate Cox proportional hazards regression showed that the study randomization was an independent correlate of FFF, along with pretreatment PSA, Gleason score, and stage. The patients who benefited most from the 8-Gy dose escalation were those with a pretreatment PSA of more than 10 ng/mL; 5-year FFF rates were 48% and 75% (P: =.011) for the 70-Gy and 78-Gy arms, respectively. There was no difference between the arms ( approximately 80% 5-year FFF) when the pretreatment PSA was < or = 10 ng/mL.
A modest dose increase of 8 Gy using conformal radiotherapy resulted in a substantial improvement in prostate cancer FFF rates for patients with a pretreatment PSA of more than 10 ng/mL. These findings document that local persistence of prostate cancer in intermediate- to high-risk patients is a major problem when doses of 70 Gy or less are used.
The cell surface receptor CD40 is required for the development of retinopathies induced by diabetes and ischemia/reperfusion. The purpose of this study was to identify signaling pathways by which ...CD40 triggers proinflammatory responses in retinal cells, since this may lead to pharmacologic targeting of these pathways as novel therapy against retinopathies.
Retinal endothelial and Müller cells were transduced with vectors that encode wild-type CD40 or CD40 with mutations in sites that recruit TNF receptor associated factors (TRAF): TRAF2,3 (ΔT2,3), TRAF6 (ΔT6), or TRAF2,3 plus TRAF6 (ΔT2,3,6). Cells also were incubated with CD40-TRAF2,3 or CD40-TRAF6 blocking peptides. We assessed intercellular adhesion molecule-1 (ICAM-1), CD40, monocyte chemoattractant protein-1 (MCP-1), VEGF, and prostaglandin E₂ (PGE₂) by fluorescence-activated cell sorting (FACS), ELISA, or mass spectrometry. Mice (B6 and CD40(-/-)) were made diabetic using streptozotocin. The MCP-1 mRNA was assessed by real-time PCR.
The CD40-mediated ICAM-1 upregulation in endothelial and Müller cells was markedly inhibited by expression of CD40 ΔT2,3 or CD40 ΔT6. The CD40 was required for MCP-1 mRNA upregulation in the retina of diabetic mice. The CD40 stimulation of endothelial and Müller cells enhanced MCP-1 production that was markedly diminished by CD40 ΔT2,3 or CD40 ΔT6. Similar results were obtained in cells incubated with CD40-TRAF2,3 or CD40-TRAF6 blocking peptides. The CD40 ligation upregulated PGE₂ and VEGF production by Müller cells, that was inhibited by CD40 ΔT2,3 or CD40 ΔT6. All cellular responses tested were obliterated by expression of CD40 ΔT2,3,6.
Blockade of a single CD40-TRAF pathway was sufficient to impair ICAM-1, MCP-1, PGE₂, and VEGF upregulation in retinal endothelial and/or Müller cells. Blockade of CD40-TRAF signaling may control retinopathies.
Summary Background Exclusive breastfeeding for at least 4 months is recommended by many governments and allergy organizations to prevent allergic disease.
Objectives To investigate whether ...exclusive breastfeeding protects against childhood eczema.
Methods Study subjects comprised 51 119 randomly selected 8‐ to 12‐year‐old schoolchildren in 21 countries. Information on eczema and breastfeeding was gathered by parental questionnaire. Children were also examined for flexural eczema and underwent skin prick testing. Odds ratios (ORs) were calculated for each study centre and then pooled across populations.
Results There was a small increase in the risk of reported ‘eczema ever’ in association with ‘breastfeeding ever’ and breastfeeding < 6 months pooled adjusted OR 1·11, 95% confidence interval (CI) 1·00–1·22 and OR 1·10, 95% CI 1·02–1·20, respectively. There was no significant association between reported ‘eczema ever’ and breastfeeding > 6 months (pooled adjusted OR 1·09, 95% CI 0·94–1·26). Risk estimates were very similar for exclusive breastfeeding < 2 months, 2–4 months and > 4 months and for eczema symptoms in the past 12 months and eczema on skin examination. As for more severe eczema, breastfeeding per se conveyed a risk reduction on sleep disturbed eczema (pooled adjusted OR 0·71, 95% CI 0·53–0·96), but this effect was lost where children had been exclusively breastfed for > 4 months (pooled adjusted OR 1·02, 95% CI 0·67–1·54). Allergic sensitization and a history of maternal allergic disease did not modify any of these findings.
Conclusions Although there was a protective effect of ever having been breastfed on more severe disease, we found no evidence that exclusive breastfeeding for 4 months or longer protects against eczema. Our results are consistent with findings from a recent systematic review of prospective studies. The U.K. breastfeeding guidelines with regard to eczema should be reviewed. Intervention studies are now required to explore how and when solids should be introduced alongside breastfeeding to aid protection against eczema and other allergic diseases.
See also the Commentary by Langan and Fewtrell
ALSUntangled #66: antimycobacterial antibiotics Pierce, Ellen S.; Barkhaus, Paul; Beauchamp, Morgan ...
Amyotrophic lateral sclerosis and frontotemporal degeneration,
07/2023, Letnik:
24, Številka:
5-6
Journal Article
Recenzirano
Odprti dostop
Several infections have been associated with motor neuron diseases resembling ALS, including species of viruses, bacteria, and parasites. Mycobacterium avium subspecies paratuberculosis (MAP), most ...known for its probable etiologic association with Crohn's disease, has been suggested as another possible infectious cause of motor neuron disease. Two published case reports describe the successful treatment of ALS-like symptoms with antimycobacterial antibiotics. Both cases had atypical features. Based on these, we believe it would be reasonable to begin performing chest imaging in PALS who have features of their history or exam that are atypical for ALS such as pain, fevers, or eye movement abnormalities. If the chest imaging is abnormal, more specific testing for mycobacteria may be indicated. Until there is more clear evidence of an association between mycobacteria and ALS, we cannot endorse the widespread use of potentially toxic antimycobacterial antibiotics for PALS.
The atmosphere of the Tula Industrial Corridor in Central Mexico is contaminated due to several industries including oil refining while station monitoring in this area are limited. Lanthanides are ...considered fingerprint of oil refinery activities, and La, Ce and Sm have been previously detected in this area using filters. The suitability of T. usneoides as a biomonitor assessing the La, Ce and Sm concentrations in Particulate Matter is evaluated by NAA. Results of both biomonitor and filters are highly correlated.
Environmental enteropathy (EE) is characterised by subclinical inflammation and hyperpermeability of the small intestine, hypothesised to be caused by recurrent ingestion of faecal bacteria. It has ...been suggested that EE may be a contributor to malnutrition and growth delays seen in children living in unsanitary conditions. We measured putative faecal EE markers myeloperoxidase (MPO) (ng/mL) and alpha-1-antitrypsin (AAT) (mg/g) in stool samples collected from 133 children aged 1–5 years in 16 communities enrolled in the WASH for WORMS randomised controlled trial in Timor-Leste. Samples were collected two years after a community-wide water, sanitation and hygiene (WASH) intervention that was integrated with regular deworming. Mixed effects multivariable linear regression models were used to examine the impact of the study intervention and of various WASH and infection-related factors on EE biomarkers. Children who lived in communities that received both the WASH intervention and deworming had similar AAT values as those who lived in communities that received only deworming (regression coefficient -0.14, p = 0.583), but they had a trend towards lower MPO values (coeff -0.51, p = 0.055). Younger children showed significantly higher MPO levels (coeff: -0.29, p = 0.002). No WASH variables or parasitic infections were associated with AAT levels. Household water being stored in covered containers was associated with lower MPO levels (coeff -1.75, p = 0.046). We found little evidence that a community-based WASH intervention had an impact on EE over a two-year period.
Immune cell dysfunction within the tumor microenvironment (TME) undermines the control of cancer progression. Established tumors contain phenotypically distinct, tumor-specific natural killer (NK) ...cells; however, the temporal dynamics, mechanistic underpinning and functional significance of the NK cell compartment remains incompletely understood. Here, we use photo-labeling, combined with longitudinal transcriptomic and cellular analyses, to interrogate the fate of intratumoral NK cells. We reveal that NK cells rapidly lose effector functions and adopt a distinct phenotypic state with features associated with tissue residency. NK cell depletion from established tumors did not alter tumor growth, indicating that intratumoral NK cells cease to actively contribute to anti-tumor responses. IL-15 administration prevented loss of function and improved tumor control, generating intratumoral NK cells with both tissue-residency characteristics and enhanced effector function. Collectively, our data reveals the fate of NK cells after recruitment into tumors and provides insight into how their function may be revived.
Asthma prevalence in children varies substantially around the world, but the contribution of known risk factors to this international variation is uncertain. The International Study of Asthma and ...Allergies in Childhood (ISAAC) Phase Two studied 8–12 year old children in 30 centres worldwide with parent-completed symptom and risk factor questionnaires and aeroallergen skin prick testing. We used multilevel logistic regression modelling to investigate the effect of adjustment for individual and ecological risk factors on the between-centre variation in prevalence of recent wheeze. Adjustment for single individual-level risk factors changed the centre-level variation from a reduction of up to 8.4% (and 8.5% for atopy) to an increase of up to 6.8%. Modelling the 11 most influential environmental factors among all children simultaneously, the centre-level variation changed little overall (2.4% increase). Modelling only factors that decreased the variance, the 6 most influential factors (synthetic and feather quilt, mother’s smoking, heating stoves, dampness and foam pillows) in combination resulted in a 21% reduction in variance. Ecological (centre-level) risk factors generally explained higher proportions of the variation than did individual risk factors. Single environmental factors and aeroallergen sensitisation measured at the individual (child) level did not explain much of the between-centre variation in wheeze prevalence.
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