Evaluation of therapeutic efficacy of Emustil drops for ocular discomfort and tear film osmolarity using different treatment management modes under dry environmental conditions.

BACKGROUND: We aimed to check the efficacy of Emustil (oil in water emulsion) drops on tear film index and ocular surface dynamics in dry environments through protection and relief treatment modalities. METHODS: The subjects were exposed to a dry environment using a Controlled Environment Chamber (CEC) where the relative humidity (RH) was 5% and the temperature was 21 °C and screened for ocular symptoms, tear osmolarity, ocular surface temperature (OST) and tear production using ocular Surface Disease Index questionnaire (OSDI), OcuSense TearLab Osmometer, FLIR System ThermaCAM P620 and Schirmer strips/phenol red test respectively. Tear production was calculated by the Tear Function Index test (TFI). RESULTS: The mean tear film osmolarity decreased significantly from 296.8 mOsm/l at 40% RH to 291 mOsm/l at 5%. (p = 0.01). Instillation of Emustil resulted in a significant increase in tear osmolarity in the relief method compared with osmolarity seen at 5% RH when no drop was used. The mean PRT value decreased from 26 ± 9 in normal conditions (40% RH) to 22 ± 4 mm in dry conditions (5% RH). Emustil drops did not induce any significant change in tear production in the PRT test. No significant change was found in OST following exposure to 5% RH. OST did not show a statistically significant change with the emulsion when used for relief (p > 0.05). The mean score of ocular discomfort observed was 70 at 5% RH. Still, the instillation of the oil-in-water emulsion (Emustil) resulted in a noticeable decrease in visual discomfort to 37 (p = 0.00) in protection and 59 in relief (p = 0.05). Emustil drops substantially improved tear film parameters under a desiccating environment, however, tear film parameters respond differently to the management modalities. In the protection method, tear film osmolarity was protected against a dry environment, while in the relief mode, tear production was improved. CONCLUSION: CEC allows for a thorough evaluation of tear film parameters and dry eye treatment protocols in labs, providing greater confidence when applying them to patients. In addition, our study showed that Emustil not only provides protection and relief for dry eyes but also helps to maintain ocular homeostasis in desiccating environments. This indicates a promising potential for improving dry eye treatment protocols.

Efficacy of hydroxypropyl-guar drops in improving tear film index and ocular surface dynamics using two treatment methods under a controlled desiccating environment.

AIM: This study aimed to assess the efficacy of hp-guar eye drops on tear film index and ocular surface dynamics under desiccating conditions using protection and relief treatment modalities. METHODOLOGY: The 12 normal, non-dry eye participants were subjected to adverse environmental conditions using a Controlled Environment Chamber (CEC) where the relative humidity (RH) was 5% and the ambient temperature was 21 °C. The participants were screened for ocular symptoms, tear osmolarity, ocular surface temperature (OST), tear production using the Ocular Surface Disease Index questionnaire (OSDI), OcuSense TearLab Osmometer, FLIR System ThermaCAM P620, and Schirmer strips. Tear production was calculated by the Tear Function Index test (TFI). RESULTS: The mean tear film osmolarity decreased significantly from 296 mOsm/L at 40% RH to 285 mOsm/L at 5% RH (p = 0.01). Conflicting responses were seen for osmolarity in protection and relief. Mean tear osmolarity was significantly higher in the protection method in comparison to the relief method (p = 0.005). The mean TFI increased from 557 at 40% to 854 at 5% (p = 0.02). A significant increase in TFI was observed in the relief method in comparison with both 40% (p = 0.001) and 5% (p = 0.04). In the relief method, the mean TFI score went up to 1139 when hp-guar was installed. A significant improvement in ocular comfort was experienced in both the protection (p = 0.041) and relief (p = 0.010) methods at 5% RH. The instillation of hp-guar drops in the relief method resulted in a significant reduction in OST. The mean OST dropped to 33.01 ºC, significantly lower than the recorded OST for both normal (p = 0.040) and dry (p = 0.014) environmental conditions. CONCLUSION: Hp-guar drops significantly improve tear film parameters under a desiccating environment, however, tear film parameters respond differently to the management modalities. In the protection method, tear film osmolarity was protected against a dry environment, while in the relief mode, an improvement in tear production and a decrease in ocular surface temperature were seen. Hp-guar performance could be maximized for the management of exposure to adverse environments by using a treatment protocol that targets the most affected parameters in each group of patients. Using CEC has the potential to provide researchers with a readily available method to evaluate the efficiency of tear supplementation.

Protecting Tear-Film Stability under Adverse Environmental Conditions Using a Mucomimetic with a Non-Newtonian Viscosity Agent.

Background and Objectives: Tamarind-seed polysaccharide (TSP) and hyaluronic acid (HA) have mucoadhesive properties that improve drug absorption and delay in drug elimination from the ocular surface. We aimed to evaluate TSP/HA-containing formulation for its efficiency in dry-eye symptoms induced by adverse environments and the interaction between mucomimic polymer and tear-film parameters. Materials and Methods: The participants were exposed to 5% relative humidity (RH) in a Controlled Environment Chamber (CEC) under constant room temperature (21 °C). Tear-film parameters were assessed at 40% RH and 5% RH. Rohto Dry Eye Relief drops were used in the two treatment modalities, protection (drops instilled before exposure to the dry environment) and relief (drops instilled after exposure to the dry environment). The HIRCAL grid, Servomed EP3 Evaporimeter, and Keeler's TearScope-Plus were used to screen for non-invasive tear break-up time (NITBUT), tear evaporation rate, and lipid-layer thickness (LLT) using protection and relief treatment methodology. Results: LLT was found to be significantly thinner at 5% RH compared with at 40% RH (p = 0.007). The median LLT dropped from 50-70 nm (grade 3) at 40% RH to 10-50 nm (grade 2) at 5% RH. TSP/HA eye drops significantly augment LLT in both treatment modalities, protection (p = 0.01) and relief (p = 0.004) at 5% RH. The mean evaporation rate doubled from 40.93 at 40% RH to 82.42 g/m2/h after exposure to 5% RH. In protection mode, the TSP/HA allowed the average evaporation rate to be much lower than when no TSP/HA was used at 5% RH (p < 0.008). No alteration in evaporation rate was recorded when the TSP/HA drop was used after exposure (relief). The mean NITBUT was reduced from 13 s in normal conditions to 6 s in the dry environment. Instillation of TSP/HA eye drops resulted in significant improvement (p = 0.006) in tear stability, where the NITBUT increased to 8 s in both protection (before exposure) and relief (after exposure) (p = 0.001). Although improved, these values were still significantly lower than NITBUT observed at 40% RH. Conclusions: Significant protection of tear-film parameters was recorded post instillation of TSP/HA eye drop under a desiccating environment. Both treatment methods (protection and relief) were shown to be effective. The presence of TSP/HA enhances the effectiveness of teardrops in protecting the tear-film parameters when exposed to adverse environments.

An update on thyroid disorders in the postpartum period.

PURPOSE: To review the pathophysiology, diagnosis and management of postpartum thyroid dysfunction, and related management of thyroid disorders during lactation. METHODS: We reviewed the literature on postpartum thyroid dysfunction and management of thyroid disorders during lactation. RESULTS: The postpartum period is characterized by a rebound from the immunotolerance induced by pregnancy. Routine thyroid function screening is not recommended for asymptomatic women in the postpartum period. Testing thyroid function should be considered at 6-12-week postpartum for high-risk populations, including women with a previous episode of postpartum thyroiditis, Graves' disease, or those with Hashimoto's thyroiditis on thyroid hormone replacement, known thyroid peroxidase antibody positivity, type 1 diabetes mellitus, other nonthyroidal autoimmune disease, or chronic hepatitis C. A serum TSH should also be checked in the setting of postpartum depression or difficulty lactating. If patients have thyrotoxicosis, new-onset or recurrent Graves' disease must be differentiated from postpartum thyroiditis, because the management differs. Periodic thyroid function testing is recommended following recovery from postpartum thyroiditis due to high lifetime risk of developing permanent hypothyroidism. Levothyroxine, and the lowest effective dose of antithyroid drugs, (propylthiouracil, methimazole, and carbimazole) can be safely used in lactating women. The use of radiopharmaceutical scanning is avoided during lactation and radioactive iodine treatment is contraindicated. CONCLUSIONS: Diagnosing postpartum thyroid dysfunction is challenging, because symptoms may be subtle. A team approach involving primary care providers, endocrinologists, and obstetricians is essential for transitioning thyroid care from the gestational to the postpartum setting.

TPO antibody in euthyroid pregnant women and cognitive ability in the offspring: a focused review.

PURPOSE: A link between maternal thyroid dysfunction during pregnancy and the risk of cognitive and behavioral problems in the offspring has previously been established; however, the potential effects of maternal thyroid autoimmunity on neurodevelopment in the absence of maternal hypothyroidism are less clear. The present review aims to highlight the gaps in knowledge in this regard and provide a thorough assessment of relevant literature. METHOD: Related keywords searched in MEDLINE, Web of Science, and Scopus till January 2021. RESULTS: There is some evidence that neuropsychological and intellectual developments of offspring are adversely affected by maternal thyroid autoimmunity, although the results of available studies are not concordant. The tools and measurements that have been applied in different studies to assess neurodevelopment or IQ vary widely and the children born to mothers with thyroid autoimmunity have been assessed at different chronological stages of life. Such variations may explain some of the differences across studies. In addition, the definition of thyroid autoimmunity has been based on TPOAb cut points provided by manufacturers in most cases, but it is preferable to define these values based on age, trimester, and method-specific reference ranges. CONCLUSION: Well-designed studies are needed to assess verbal and non-verbal neurocognition of offspring born to mothers with autoimmune thyroid disease before or during pregnancy.

Do people perceive benefits in the use of social prescribing to address loneliness and/or social isolation? A qualitative meta-synthesis of the literature.

Social prescribing is a means by which clinical services can link individuals who have psychological, social and/or practical needs with non-clinical services within their local community. There is a lack of empirical evidence investigating whether social prescribing helps such individuals and which interventions are the most effective and accepted by them to address their loneliness. This meta-synthesis aimed to synthesise findings from qualitative studies exploring experiences of people (of any age) who participated in any social prescribing intervention aimed at loneliness and/or social isolation to ascertain whether they felt it helped address loneliness/isolation and the potential mechanisms by which this might occur. We conducted a systematic search of 5 electronic databases and 4 other databases that would yield grey literature in April 2021 to identify qualitative articles on this topic written in English or French. We assessed the quality of the included studies using recognised tools, and synthesised findings using the approach of thematic analysis. We identified 19 records analysed (e.g. journal articles) from 18 studies meeting inclusion criteria. Our analysis identified three themes: (1) increased sense of wellbeing (with six subthemes), (2) factors that engendered an ongoing desire to connect with others, and (3) perceived drawbacks of social prescribing. These themes illustrate the benefits and difficulties people perceive in social prescribing programmes addressing loneliness and social isolation, with an overall balance of more benefits than drawbacks in social prescribing participation. However, given the unhelpful aspects of social prescribing identified by some participants, greater thought should be given to potential harms. Moreover, further qualitative and quantitative research is needed to better understand mechanisms and effectiveness, and how different components of social prescribing might be best matched to individual participants.

The unmet need for better risk stratification of non-proliferative diabetic retinopathy.

Diabetic retinopathy is a common microvascular complication of diabetes and remains one of the leading causes of preventable blindness in working-age people. Non-proliferative diabetic retinopathy is the earliest stage of diabetic retinopathy and is typically asymptomatic. Currently, the severity of diabetic retinopathy is assessed using semi-quantitative grading systems based on the presence or absence of retinal lesions. These methods are well validated, but do not predict those at high risk of rapid progression to sight-threatening diabetic retinopathy; therefore, new approaches for identifying these people are a current unmet need. We evaluated published data reporting the lesion characteristics associated with different progression profiles in people with non-proliferative diabetic retinopathy. Based on these findings, we propose that additional assessments of features of non-proliferative diabetic retinopathy lesions may help to stratify people based on the likelihood of rapid progression. In addition to the current classification, the following measurements should be considered: the shape and size of lesions; whether lesions are angiogenic in origin; the location of lesions, including predominantly peripheral lesions; and lesion turnover and dynamics. For lesions commonly seen in hypertensive retinopathy, a detailed assessment of potential concomitant diseases is also recommended. We believe that natural history studies of these changes will help characterize these non-proliferative diabetic retinopathy progression profiles and advance our understanding of the pathogenesis of diabetic retinopathy in order to individualize management of people with diabetic retinopathy.

Association of Thyroid Function Test Abnormalities and Thyroid Autoimmunity With Preterm Birth: A Systematic Review and Meta-analysis.

Importance: Maternal hypothyroidism and hyperthyroidism are risk factors for preterm birth. Milder thyroid function test abnormalities and thyroid autoimmunity are more prevalent, but it remains controversial if these are associated with preterm birth. Objective: To study if maternal thyroid function test abnormalities and thyroid autoimmunity are risk factors for preterm birth. Data Sources and Study Selection: Studies were identified through a search of the Ovid MEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and Google Scholar databases from inception to March 18, 2018, and by publishing open invitations in relevant journals. Data sets from published and unpublished prospective cohort studies with data on thyroid function tests (thyrotropin [often referred to as thyroid-stimulating hormone or TSH] and free thyroxine [FT4] concentrations) or thyroid peroxidase (TPO) antibody measurements and gestational age at birth were screened for eligibility by 2 independent reviewers. Studies in which participants received treatment based on abnormal thyroid function tests were excluded. Data Extraction and Synthesis: The primary authors provided individual participant data that were analyzed using mixed-effects models. Main Outcomes and Measures: The primary outcome was preterm birth (<37 weeks' gestational age). Results: From 2526 published reports, 35 cohorts were invited to participate. After the addition of 5 unpublished data sets, a total of 19 cohorts were included. The study population included 47 045 pregnant women (mean age, 29 years; median gestational age at blood sampling, 12.9 weeks), of whom 1234 (3.1%) had subclinical hypothyroidism (increased thyrotropin concentration with normal FT4 concentration), 904 (2.2%) had isolated hypothyroxinemia (decreased FT4 concentration with normal thyrotropin concentration), and 3043 (7.5%) were TPO antibody positive; 2357 (5.0%) had a preterm birth. The risk of preterm birth was higher for women with subclinical hypothyroidism than euthyroid women (6.1% vs 5.0%, respectively; absolute risk difference, 1.4% [95% CI, 0%-3.2%]; odds ratio [OR], 1.29 [95% CI, 1.01-1.64]). Among women with isolated hypothyroxinemia, the risk of preterm birth was 7.1% vs 5.0% in euthyroid women (absolute risk difference, 2.3% [95% CI, 0.6%-4.5%]; OR, 1.46 [95% CI, 1.12-1.90]). In continuous analyses, each 1-SD higher maternal thyrotropin concentration was associated with a higher risk of preterm birth (absolute risk difference, 0.2% [95% CI, 0%-0.4%] per 1 SD; OR, 1.04 [95% CI, 1.00-1.09] per 1 SD). Thyroid peroxidase antibody-positive women had a higher risk of preterm birth vs TPO antibody-negative women (6.6% vs 4.9%, respectively; absolute risk difference, 1.6% [95% CI, 0.7%-2.8%]; OR, 1.33 [95% CI, 1.15-1.56]). Conclusions and Relevance: Among pregnant women without overt thyroid disease, subclinical hypothyroidism, isolated hypothyroxinemia, and TPO antibody positivity were significantly associated with higher risk of preterm birth. These results provide insights toward optimizing clinical decision-making strategies that should consider the potential harms and benefits of screening programs and levothyroxine treatment during pregnancy.

Effect of tear supplements on signs, symptoms and inflammatory markers in dry eye.

PURPOSE: Three tear supplements were compared for their effects on the signs, symptoms and inflammatory status of subjects with dry eye disease. Assessments were made before and after both 2 and 4 weeks of treatment. METHODS: In this masked, randomized, 3-way crossover trial, eighteen dry eye subjects were recruited. At each visit, symptoms, tear evaporation rate, stability and osmolarity were measured and tear samples were analyzed for 7 inflammatory markers, using multiplex immunoassays. The 3 treatments included carboxymethylcellulose-glycerine-castor oil (CGC), carboxymethylcellulose (CMC) and hydroxypropyl guar (HPG). The CGC and HPG drops are emulsified lipids; CGC also contains osmoprotectants. The CMC drop is a standard aqueous polymeric supplement. RESULTS: Significant improvements were seen in symptoms (OSDI) and tear stability (NITBUT) with all 3 treatments at 4 weeks. At 4 weeks post-CGC, 6 out of 7 biomarkers demonstrated a >25% reduction (in 40% of subjects). The same reduction (>25%) was seen in 10% of the subjects for CMC and in none of the subjects for HPG. No significantly different change to either evaporation rate or tear osmolarity was found following any of the three treatments. CONCLUSIONS: In this study, the CGC treatment resulted in the greatest reduction in ocular biomarkers of inflammation, while all 3 treatments reduced symptoms and improved tear stability. These results indicate that subject-perceived symptomatic improvements are not necessarily associated with a reduction in objective measures of inflammation.

Effect of Ambient Temperature on the Human Tear Film.

PURPOSE: During everyday life, the tear film is exposed to a wide range of ambient temperatures. This study aims to investigate the effect of ambient temperature on tear film physiology. METHOD: A controlled environment chamber was used to create different ambient temperatures (5, 10, 15, 20, and 25°C) at a constant relative humidity of 40%. Subjects attended for two separate visits and were exposed to 25, 20, and 15°C at one visit and to 10 and 5°C at the other visit. The subjects were exposed to each room temperature for 10 min before investigating tear film parameters. The order of the visits was random. Tear physiology parameters assessed were tear evaporation rate, noninvasive tear break-up time (NITBUT), lipid layer thickness (LLT), and ocular surface temperature (OST). Each parameter was assessed under each condition. RESULT: A threefold increase in tear evaporation rate was observed as ambient temperature increased to 25°C (P=0.00). The mean evaporation rate increased from 0.056 µL/min at 5°C to 0.17 µL/min at 25°C. The mean NITBUT increased from 7.31 sec at 5°C to 12.35 sec at 25°C (P=0.01). A significant change in LLT was also observed (P=0.00), LLT median ranged between 20 and 40 nm at 5 and 10°C and increased to 40 and 90 nm at 15, 20, and 25°C. Mean reduction of 4°C OST was observed as ambient temperature decreased from 25 to 5°C. CONCLUSION: Ambient temperature has a considerable effect on human tear film characteristics. Tear evaporation rate, tear LLT, tear stability, and OST were considerably affected by ambient temperature. Chronic exposure to low ambient temperature would likely result in symptoms of dry eye and ultimately ocular surface disorders.

Development and application of spherically curved charge-coupled device imagers.

Operation of a CCD imager on a curved focal surface offers advantages to flat focal planes, especially for lightweight, relatively simple optical systems. The first advantage is that the modulation transfer function can approach diffraction-limited performance for a spherical focal surface employed in large field-of-view or large-format imagers. The second advantage is that a curved focal surface maintains more uniform illumination as a function of radius from the field center. Examples of applications of curved imagers, described here, include a small compact imager and the large curved array used in the Space Surveillance Telescope. The operational characteristics and mechanical limits of an imager deformed to a 15 mm radius are also described.

Imaging trematode and nematode parasites.

Recent advances in molecular genetics and in imaging mean that it is now increasingly feasible to image biological processes within helminth parasites and to visualize interactions between worms and their hosts. Moreover, other innovative imaging approaches that are not dependent on transgenic parasites have been applied to, and or developed for, the study of helminth parasites and have provided novel and important insights into the biology of these important pathogens.

Oxidative stress, inflammation, and muscle soreness in an 894-km relay trail run.

We describe the effects of multi-day relay trail running on muscle soreness and damage, and systemic immune, inflammatory, and oxidative responses. 16 male and 4 female athletes ran 894 km in 47 stages over 95 h, with mean (SD) 6.4 (1.0) stages per athlete and 19.0 (1.7) km per stage. We observed post-pre run increases in serum creatine kinase (qualified effect size extremely large, p = 0.002), IL-6 (extremely large, p < 0.001), urinary 8-isoprostane/creatinine (extremely large, p = 0.04), TNF-α (large, p = 0.002), leukocyte count (very large, p < 0.0001) and neutrophil fraction (very large, p < 0.001); and reductions in hemoglobin (moderate, p < 0.001), hematocrit (moderate, p < 0.001), and lymphocyte fraction (trivial, p < 0.001). An increase in ORAC total antioxidant capacity (TAC, small, p = 0.3) and decrease in urinary 8-OHdG/creatinine (small, p = 0.1) were not statistically significant. During the run, muscle soreness was most frequent in the quadriceps. The threshold for muscle pain (pain-pressure algometry) in the vastus lateralis and gastrocnemius was lower post-run (small, p = 0.04 and 0.03). Average running speed was correlated with algometer pain and leukocyte count (large, r = 0.52), and TAC was correlated with IL-6 (very large, r = 0.76) and 8-isoprostane/creatinine (very large, r = -0.72). Multi-day stage-racing increases inflammation, lipid peroxidation, muscle damage and soreness without oxidative DNA damage. High TAC is associated with reduced exercise-induced lipid peroxidation, but is not related to immune response or muscle damage.

A pilot study on the combination treatment of reduced-fluence photodynamic therapy, intravitreal ranibizumab, intravitreal dexamethasone and oral minocycline for neovascular age-related macular degeneration.

AIM: To assess the safety and efficacy of the combined treatment of reduced-fluence verteporfin photodynamic therapy (PDT), intravitreal ranibizumab, intravitreal dexamethasone and oral minocycline for choroidal neovascularisa- tion (CNV) secondary to age-related macular degeneration (AMD). METHODS: Nineteen patients with subfoveal CNV secondary to AMD were recruited into the trial. All study eyes (n = 19) received a single cycle of reduced-fluence (25 mJ/cm(2)) PDT with verteporfin followed by an intravitreal injection of ranibizumab 0.3 mg/0.05 ml and dexamethasone 200 µg at baseline. Oral minocycline 100 mg daily was started the following day and continued for 3 months. Patients were followed up monthly for 12 months. Repeat intravitreal ranibizumab was given if best-corrected visual acuity (BCVA) deteriorated by >5 letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart or central retinal thickness (CRT) on ocular coherence tomography increased >100 µm. RESULTS: Eighteen patients completed the 12-month study. Stable vision (loss of ≤15 ETDRS letters) was maintained in 89% eyes (16/18). The mean change in BCVA was -5.0 ± 10.5 ETDRS letters. The mean number of ranibizumab injections was 3.4 (range 2-6). The mean reduction in the CRT was 66.3 µm (±75). CONCLUSION: This open-label clinical trial has demonstrated the safety in terms of adverse effects and maintenance of stable vision of combination treatment with verteporfin, ranibizumab, dexamethasone and minocycline in exudative AMD. However, the outcomes with reduced-fluence PDT combination therapy does not differ significantly with outcomes of clinical trials on combination treatment with standard dose PDT and intravitreal ranibizumab in neovascular AMD.

Immunoregulation of cutaneous leishmaniasis. T cell lines that transfer protective immunity or exacerbation belong to different T helper subsets and respond to distinct parasite antigens.

BALB/c mice can be protected against a normally fatal Leishmania major infection by immunization with a partially purified, soluble subfraction of the parasite (fraction 9). In this study, we demonstrate that a T cell line established against fraction 9, designated line 9, transfers protection equivalent to that obtained by active immunization. In contrast, T cell lines (lines 1 and 9.2) responsive to a nonprotective soluble fraction (fraction 1) not only failed to protect BALB/c mice against L. major, but exacerbated the infection. Most importantly, in addition to differing in their antigen specificity, protective and exacerbative T cells lines could be distinguished on the basis of the lymphokines produced, a characteristic previously used to separate murine Th cells into two subsets, designated Th1 and Th2. We found that the protective cell line, line 9, displayed the Th1 property of secreting IL-2 and IFN-gamma, while the exacerbating lines secreted IL-4 and IL-5, a characteristic of Th2 cells. Our results demonstrate that Th1 and Th2 cells may have dramatically different effects on the outcome of an infection, and suggest that susceptibility and resistance in experimental leishmaniasis may depend upon a balance between the Th subsets induced.

Schistosoma mansoni egg-induced early IL-4 production is dependent upon IL-5 and eosinophils.

The initial immune response to Schistosoma mansoni eggs presumably results in IL-4 production, as schistosome eggs are strong Th2-inducing antigens and the differentiation of antigen-specific Th2 cells is largely dependent on the presence of IL-4 during priming of naive Th cells. Consistent with this concept, intraperitoneal injection of mice with schistosome eggs results in an upregulation of IL-4 production by peritoneal exudate cells (PECs) within 12 h. Egg-induced IL-4 is rapidly bound by its receptor, suggesting that this cytokine is utilized by a cell type present at the site of antigen deposition or is complexed to soluble receptor. The peak of early IL-4 production is accompanied by a local eosinophilia and the apparent disappearance of mast cells. Studies utilizing either IL-4, IL-5, or mast cell-deficient mice indicate that the eosinophilia is dependent on mast cells and IL-5 and independent of IL-4. Strikingly, egg-induced IL-4 production is absent in animals lacking the early peritoneal eosinophilia. Immunocytochemical analysis of PEC following egg injection indicates that the eosinophils themselves make IL-4. These data strongly suggest that egg-induced IL-5 plays an essential role in recruiting eosinophils to the site of antigen deposition and that it is these eosinophils that then directly produce early IL-4.

Downregulation of Th1 cytokine production accompanies induction of Th2 responses by a parasitic helminth, Schistosoma mansoni.

In the mouse, infection with Schistosoma mansoni results in an egg-producing infection and associated disease, whereas vaccination with attenuated larval stages produces a substantial and specific immunity in the absence of egg-induced pathology. Preliminary data showing enhanced interleukin-5 (IL-5) production by T cells from infected mice and interferon gamma (IFN-gamma) synthesis by cells from vaccinated animals (7), suggested differential CD4+ subset stimulation by the different parasite stimuli. To confirm this hypothesis, lymphocytes from vaccinated or infected animals were compared for their ability to produce IFN-gamma and IL-2 (secreted by Th1 cells) as compared with IL-4 and IL-5 (characteristic Th2 cytokines). After stimulation with specific antigen or mitogen, T cells from vaccinated mice or prepatently infected animals responded primarily with Th1 lymphokines, whereas lymphocytes from patently infected mice instead produced Th2 cytokines. The Th2 response in infected animals was shown to be induced by schistosome eggs and directed largely against egg antigens, whereas the Th1 reactivity in vaccinated mice was triggered primarily by larval antigens. Interestingly, Th1 responses in mice carrying egg-producing infections were found to be profoundly downregulated. Moreover, the injection of eggs into vaccinated mice resulted in a reduction of antigen and mitogen-stimulated Th1 function accompanied by a coincident expression of Th2 responses. Together, the data suggest that coincident with the induction of Th2 responses, murine schistosome infection results in an inhibition of potentially protective Th1 function. This previously unrecognized downregulation of Th1 cytokine production may be an important immunological consequence of helminth infection related to host adaptation.

The influence of automobile windscreen rake on effective light transmittance.

The theoretical transmittances at the installation angle of the windscreens of the ten best-selling cars in the UK in 2008 are investigated. The data show that the ten most popular cars on the UK roads have a windscreen rake that reduces transmittance to a value close to or below that specified in International Standards for normal incidence. British and International Standards for windscreen transmittance should be revisited by the relevant authorities in the light of the high rake angles that have become widespread in recent years. The problem is worsened considerably by tinted windscreens having become the default option in many models. It is also suggested that there may be good reason for all spectacles supplied to drivers for low light level driving to be untinted and anti-reflection coated.

Strip meniscometry tube: a rapid method for assessing aqueous deficient dry eye.

BACKGROUND: The aim of this study was to investigate the utility of strip meniscometry tube (SMTube) for the quantitative assessment of the tear film, by comparing it to measurements of tear turnover rate using the gold standard method, fluorophotometry. Also, to determine the viability of this test as a diagnostic tool for aqueous deficient dry eye (ADDE), to inform appropriate clinical management. METHODS: Thirty-two participants (15 ADDE; 17 non-ADDE) were recruited. Tear turnover rate of the right eye of each subject was conducted with an automated scanning fluorophotometer and SMTube test was conducted. Tear meniscus height was assessed using a slitlamp biomicroscope and eyepiece graticule. RESULTS: Significant differences between the ADDE and the non-ADDE groups were found for all measures: tear turnover rate 7.9 ± 1.8 versus 19.6 ± 5.9 per cent/minute (p < 0.001), SMTube 3.2 ± 1.1 versus 5.7 ± 2.3 mm (p = 0.001) and tear meniscus height 0.18 ± 0.05 versus 0.23 ± 0.04 mm (p = 0.004). Moreover, significant correlations were found between tear turnover rate and SMTube (rho = 0.78, p < 0.001), tear turnover rate and tear meniscus height (rho = 0.54, p < 0.001) and SMTube and tear meniscus height (rho = 0.47, p < 0.01). Using a receiver operating characteristic curve, SMTube showed a sensitivity of 67 per cent and a specificity of 88 per cent for the diagnosis of ADDE. CONCLUSION: Given its performance, availability, speed and the fact it is relatively cheap, the study shows that the SMTube can be used as an alternative to fluorophotometry to assess tear production. It appears from the results that SMTube is a viable minimally invasive test for the diagnosis of ADDE.

Identification of paramyosin as schistosome antigen recognized by intradermally vaccinated mice.

Mice immunized intradermally with extracts of Schistosoma mansoni in combination with the adjuvant BCG are significantly protected against subsequent infection with living larval forms of the parasite. Remarkably, these vaccinated animals produce antibodies predominantly against a single parasite protein of molecular weight 97 kilodaltons (Sm-97). A complementary DNA that encodes about half of the Sm-97 molecule has now been cloned and sequenced. Analysis of the deduced amino acid sequence reveals a protein containing periodic repeats of hydrophobic amino acids characteristic of an alpha-helical coiled-coil structure. The deduced amino acid composition of the cloned gene and several properties of the native protein are similar to that of paramyosin, an alpha-helical protein that forms the core for myosin filaments in invertebrate muscle. Paramyosin was isolated from Schistosoma mansoni adult worms and antibodies to Sm-97 were shown to react with this molecule as well as with a known paramyosin from molluscan muscle.