Bovine Meissner-like corpuscle and evolutionary ecology of mammalian somatosensory acuity.

The mammalian snout has Meissner's corpuscles (MCs), which transmit epicritic sensations as the animal explores its surroundings. To comprehend the somatosensory acuity in mammals, we examined the structural organization and density of bovine Meissner-like corpuscles (BMLCs) at various ages and compared the changes with other mammalian MCs. The skin from the snout of cows or oxen (2-11 years old) was obtained and processed through routine histological technique. Five-µm thick sections were prepared, silver stained according to the Bielschowsky technique as modified by Winkelman and Schmidt (Mayo Clinic Proceedings, 1957, 217), and observed under a compound light microscope quantitatively and qualitatively. The glabrous skin of the cow snout consisted of two types of BMLCs: One was a cylindrical or elongated structure found in the dermal papillae. The other type was spherical and developed in the superficial layers of the epidermis. BMLCs consisted of both coarse and fine nerve fibres. In the young, the corpuscle comprised thin nerve fibres with indistinct cell outlines. In adults, nerve fibres in the corpuscles were closely packed, and networks, varicosities and end bulbs were well developed. With advancing age, the MCs attenuated into a disorganized mass of nerve fibres. The bovine snout is a highly evolved somatosensory organ due to its rich nerve supply and functionally resembles the anthropoid fingertip. Somatosensory acuity will be lower in the glabrous bovine skin than in primate glabrous skin of the fingertip, as the nerve terminals within the BMLCs are less elaborate in content and structural complexity.

Post-licensure observational safety study after meningococcal B vaccine 4CMenB (Bexsero) vaccination within the routine UK immunisation program.

The study investigated the safety of 4-component meningococcal serogroup B vaccination (4CMenB) in routine care. 4CMenB exposure and seizures, febrile seizures and Kawasaki disease were identified from The Health Improvement Network (THIN) database of UK electronic primary healthcare records, 2015-2018. A self-controlled case series analysis was completed. Anaphylaxis, Guillain-Barré syndrome and acute disseminated encephalomyelitis were secondary outcomes. A total of 107,231 children aged 1-18 months received ≥1 doses of 4CMenB vaccination. Most 4CMenB exposure (93%) was on the same day as other vaccines within a complete national immunisation program stage. With day 0 as day of vaccination, 43 seizures occurred in days 0-6 after 239,505 doses, and 23 febrile seizures occurred in days 0-6, and 4 Kawasaki disease cases in days 1-28 after 194,929 4CMenB doses. Adjusted incidence rate ratios including all 4CMenB exposures were 1.43 (95%CI: 1.02-2.02) for seizures and 1.72 (95%CI: 1.08-2.75) for febrile seizures. There were insufficient cases to model Kawasaki disease, and no cases of the secondary outcomes in risk periods when they may be associated with the vaccination. This study shows few cases of the outcomes after vaccination including 4CMenB with an increased risk of seizures and febrile seizures. It is not possible to attribute the finding to one specific vaccination as the majority of 4CMenB was given with other vaccinations. Trial registration: NA.

5 year incidence of YAG capsulotomy and PCO after cataract surgery with single-piece monofocal intraocular lenses: a real-world evidence study of 20,763 eyes.

OBJECTIVES: To evaluate the 3- and 5-year incidence of posterior capsule opacification (PCO) and neodymium-doped yttrium aluminium garnet (Nd:YAG) capsulotomy in patients following cataract surgery, comparing results for different single-piece acrylic hydrophilic and hydrophobic monofocal intraocular lens (IOL) models and other patient factors. PATIENTS AND METHODS: Electronic medical record data collected from seven United Kingdom (UK) National Health Service (NHS) ophthalmology clinics for routine, age-related (≥65 years) cataract surgeries that implanted single-piece acrylic monofocal IOLs during 2010-2013 were used to calculate 3- and 5-year incidence of Nd:YAG and PCO. IOL models of Alcon Acrysof, AMO Tecnis, Bausch & Lomb (B & L) Akreos, LenStec Softec, and Rayner Flex were analyzed. Pairwise comparisons were conducted between AcrySof IOLs and other IOLs using Bonferroni adjustment for multiplicity. Multivariate analyses were conducted adjusting for known confounders. RESULTS: The incidence of Nd:YAG capsulotomy ranged between 2.4-12.6% at 3 years and 5.8-19.3% at 5 years post-cataract surgery. Similarly, the incidence of PCO ranged between 4.7-18.6% at 3 years and 7.1-22.6% at 5 years. When comparing all of the single-piece IOLs, AcrySof demonstrated the lowest incidence rates for both PCO and Nd:YAG (P < 0.001 for each comparison). From adjusted logistic regression analysis, AcrySof were associated with lower 3- and 5-year odds of Nd:YAG and PCO incidence. CONCLUSIONS: Following cataract surgery with single-piece monofocal IOLs different incidence rates of PCO were observed with different IOLs. AcrySof IOLs were associated with significantly lower incidence of PCO requiring Nd:YAG treatment over periods of 3 and 5 years.

Choice of time period to identify confounders for propensity score matching, affected the estimate: a retrospective cohort study of drug effectiveness in asthmatic children.

OBJECTIVES: To control for confounding by indication in comparative (drug) effectiveness studies, propensity score (PS) methods may be used. Since childhood diseases or outcomes often present as acute events, we compared the effect of using different look-back periods in electronic health-care data, to construct PSs. This was applied in our research on the effect of a combination of inhaled corticosteroids/long-acting beta-2 agonists (ICS + LABA), either as fixed combination or used as loose combination (2 separate inhaler devices) in the prevention of severe asthma exacerbations. METHODS: We created a cohort of children (5-17 years) diagnosed with asthma from the Dutch Integrated Primary Care information database. Within this cohort, we identified new users of ICS + LABA, either as fixed combination or loose combination (2 separate inhaler devices). The outcome of interest was severe asthma exacerbations. PSs for type of treatment were created using comorbidity and drug use history in different time windows: 1 week, 1 month, 3 months, 1 year, and full history prior to the start of treatment. PSs were used for matching subjects in both exposure groups. Time to first asthma exacerbation was analyzed with Cox proportional hazard regression. The results were compared with published clinical trials. RESULTS: Of 39,682 asthmatic children, 3,500 (8.8%) were new users of either ICS + LABA fixed (3,324 [95.0%]) or loose (176 [5.0%]). The crude hazard ratio (HR) for a severe asthma exacerbation, comparing ICS + LABA fixed to loose was 0.37 (95% confidence interval [CI]: 0.20-0.66). PS-matched HRs (1 week, 1 month, 3 month, 1 year, and full history) were 0.48 (95% CI: 0.22-1.04); 0.60 (95% CI: 0.26-1.38), 0.69 (95% CI: 0.31-1.57), 0.56 (CI: 0.25-1.24), and 0.58 (CI: 0.24-1.36), respectively. CONCLUSIONS: PS matching can be used to control for confounding in pediatric comparative (drug) effectiveness studies, the impact of different look-back periods to implement the PS is important. Controlling for confounders occurring in the 3 months preceding drug exposure may yield results comparable to clinical trial results.

Effect of spacer length of alkanediyl-alpha,omega-bis(dimethylcetylammonium bromide) gemini homologues on the interfacial and physicochemical properties of BSA.

The interactions of bovine serum albumin (BSA) with cationic gemini surfactants alkanediyl-alpha,omega-bis(dimethylcetylammonium bromide) (designated as C(16)C(s)C(16)Br(2), s=4, 5, and 6) and single chain surfactant cetyltrimethylammonium bromide (CTAB) have been investigated with tensiometry, Rayleigh's scattering, fluorescence spectroscopy, and circular dichroism at physiological pH and 25 degrees C. The results of the multi-technique approach showed that the gemini surfactants interact more efficiently with the proteins than their conventional single chain counterparts and their efficiency increases with decrease in the length of the spacer. The saturation in interfacial tension occurred at a lower concentration in presence of BSA compared to CMC of the surfactants in absence of BSA and the concentration of gemini surfactants corresponding to interfacial saturation decreases with decrease in the spacer length. Fluorescence and circular dichroism spectroscopy results revealed increase in unfolding of BSA with decrease in spacer length of gemini surfactants.

Interaction of bovine serum albumin with cationic single chain+nonionic and cationic gemini+nonionic binary surfactant mixtures.

The interaction of bovine serum albumin (BSA) with cetyltrimethylammonium bromide (CTAB), C(16)C(4)C(16)Br(2), Brij58, and their binary mixtures has been studied using tensiometry, spectrofluorometry, and circular dichroism at physiological pH and 25 degrees C. The tensiometric profiles of CTAB and C(16)C(4)C(16)Br(2) in the presence of BSA exhibit a single break at a lower surfactant concentration termed as C(1) (concentration corresponding to saturation of the interface) compared to their critical micelle concentration (CMC) in the buffered solution. However, for Brij58, CTAB+Brij58, and C(16)C(4)C(16)Br(2)+Brij58, two breaks were observed, first at the critical aggregation concentration (CAC), corresponding to onset of interaction with BSA and the second at C(1) corresponding to saturation of the interface. The interaction of CTAB+Brij58 and C(16)C(4)C(16)Br(2)+Brij58 mixtures with the BSA solution is discussed in terms of competition between surfactant-surfactant and surfactant-BSA interactions. CTAB+Brij58 and C(16)C(4)C(16)Br(2)+Brij58 mixtures show nonideality with respect to mixed micelle formation, which is reflected in their interaction with the BSA. The interaction of CTAB+Brij58 with BSA decreases with increase in the mole fraction of CTAB in the mixture, whereas in C(16)C(4)C(16)Br(2)+Brij58 the reverse is the case. The results of the present study may prove fruitful in optimizing the properties of surfactant-protein mixtures relevant for many formulations.

Bilateral 'vitelliform-like' macular lesions in a patient with multiple myeloma.

A 73-year-old woman was referred to the eye clinic in February 2005 with reduced vision in both eyes. On examination, her visual acuity was 20/40, N6 right eye and 20/64, N6 left eye. Bilateral unusual 'vitelliform-like' lesions at the macula (accumulation of yellow material in the subretinal space), which demonstrated blocked fluorescence on fluorescein angiography and a lack of increased autofluorescence signal on fundus autofluorescence imaging, were detected. The patient was followed-up until April 2007 when retinal haemorrhages were detected and blood work-up was undertaken; during this follow-up period the material present at the macula progressively disappeared. As a result of the blood work-up, the diagnosis of multiple myeloma was established; the macular lesions were thought to relate to the latter disease and represent subretinal deposition of immunoglobulin.

The role of botulinum toxin in decompensated strabismus.

BACKGROUND: The surgical management of decompensated strabismus is well described. Conservative treatment may employ the use of lenses and prisms. However, the use of botulinum toxin in decompensated squint is poorly documented. In these patients, with the potential for fusion, botulinum toxin may serve to stabilize the ocular alignment by bringing the images within the fusion range. PURPOSE: The aim of this study was to assess the role of botulinum toxin in the treatment of decompensated squints. METHODS: A retrospective case series involving 92 patients with decompensated squints between December 1990 and July 2005. Botulinum toxin was injected into the lateral rectus in 45 cases and into the medial rectus in 47. This was performed under local anesthesia in 74 cases, the remainder with ketamine anesthesia. Patients were assessed preoperatively at 2 weeks, 4 months, and a minimum of 12 months postoperatively. We defined successful treatment where the resultant stabilized deviation was less than or equal to 10 prism diopters with resolution of diplopia. RESULTS: In this study, 47 patients had a decompensated microesotropia and 45 had a decompensated exophoria. We found that 27 (29.3%) patients were asymptomatic following injection of botulinum toxin. Fourteen (15.2%) patients were better controlled and did not require further intervention. Subsequent surgery was performed in 45 patients (48.9%). CONCLUSION: Our results suggest almost half of those patients requiring treatment for decompensated squint benefit from botulinum toxin, without requiring surgical intervention. This approach is less invasive and allows potential for recovery of binocular function.

Botulinum toxin injection for postoperative diplopia testing in adult strabismus.

PURPOSE: To investigate the use of botulinum toxin type A in identifying adult patients with constant strabismus who are at high risk of developing intractable diplopia after surgery. METHODS: A retrospective review of adult patients with constant horizontal strabismus who had botulinum toxin injection to evaluate their risk of postoperative diplopia. These patients reported diplopia when prisms were used to neutralize the deviation. RESULTS: One hundred ninety-five adults were studied; their mean age was 40.3 +/- 14 years (range, 16 to 73 years). One hundred thirty-three (68%) had botulinum toxin injected into a lateral rectus muscle; 62 (32%) had injections in a medial rectus muscle. Only 14 (7%) developed diplopia; 9 (4.6%) of these had troublesome diplopia but 5 (2.6%) could cope with the double vision and elected to have surgery. Surgical correction was recommended to the remaining 181 (93%) who did not experience diplopia. Complications of botulinum toxin injection were ptosis (10 patients, 5.1%) and superior oblique muscle weakness (3 patients, 1.5%). Twenty-six patients (13.3%) had a poor response to the first injection and required a second injection with a double dose. Surgery did not result in intractable diplopia after 6 weeks in any patient with a negative botulinum toxin diplopia test. CONCLUSIONS: Botulinum toxin is a useful diagnostic tool for identifying patients with a low risk or no risk of postoperative diplopia despite a positive prism diplopia test.

Glycaemic control and control of risk factors in diabetes patients in an ophthalmology clinic: what lessons have we learned from the UKPDS and DCCT studies?

PURPOSE: The Diabetes Control and Complications Trial (DCCT) and UK Prospective Diabetes Study (UKPDS) have studied glycaemic control as well as other risk factors in preventing the progression of diabetic end-organ disease, including diabetic retinopathy. We wished to determine to what extent a cross-section of diabetes patients attending our eye clinic met the targets laid down by recent landmark studies. METHODS: We prospectively assessed 44 consecutive diabetes patients attending outpatient clinics for assessment of diabetic retinopathy. Each patient had HbA1c levels, serum cholesterol and blood pressure checked. A proforma was completed for each patient. RESULTS: Of the 44 patients studied, 11 had type 1 diabetes mellitus (DM) and 33 had type 2 DM (11 insulin-dependent DM [IDDM], 22 non-insulin-dependent DM [NIDDM]). The mean age of type 1 DM patients was 43 years; that of type 2 DM patients was 62 years. Five of 11 (46%) type 1 DM patients had poorly controlled diabetes (HbA1c > 9%) compared with four of 33 (12%) type 2 DM patients. Overall, 27 of 44 (62%) patients were on antihypertensive medication. The prevalence of poorly controlled blood pressure (> 150/85 mmHg treated; > 160/90 mmHg untreated) was 16 of 44 (36%) patients overall, and was higher for type 2 DM patients (13/33, 39%) than for type 1 DM patients (3/11, 27%). Random serum cholesterol levels > 5.2 were found in 10 of 44 (23%) patients overall (4/11 [36%] type 1 and 6/33 [18%] type 2 DM patients). CONCLUSIONS: Control of HbA1c, hypertension and hypercholesterolaemia can slow progression of retinopathy and other DM end-points. Many of our patients were poorly controlled in terms of these risk factors. More attention should be addressed to these primary preventative factors in the management of diabetes patients.

Unaugmented vertical muscle transposition surgery for chronic sixth nerve paralysis.

INTRODUCTION: Chronic sixth nerve palsy can cause incapacitating diplopia requiring vertical muscle transposition surgery. Augmentation of surgery, with lateral fixation sutures, medial rectus recession or botulinum toxin injection, is associated with an increased risk of complications. PURPOSE: Our aim was to evaluate the efficacy and safety of unaugmented full-tendon vertical rectus transposition in chronic sixth nerve paralysis. METHODS: Longitudinal study of 21 patients with chronic sixth nerve paralysis of longer than 6 months duration, who underwent superior and inferior recti transposition surgery without medial rectus recession or botulinum toxin injection. Details of surgery, preoperative and postoperative examinations including full orthoptic examination were obtained from an electronic database. Outcomes included the change in angle of deviation, the requirement for further surgery to the medial rectus and postoperative improvement in diplopia. SPSS software (Version 12.0.1, SPSS Inc. Chicago, IL) was used to summarize baseline characteristics and outcomes and to compare preoperative and postoperative deviation (paired t-test). RESULTS: Twenty-one patients (10 (47.6%) men and 11 (52.4%) women) with a mean age of 41 years (range 4 to 74 years) were operated in the period between April 1998 and November 2000. Eighteen patients had unilateral and three had bilateral acquired sixth nerve palsy. Nineteen patients required unilateral surgery and two had bilateral transposition procedures. In patients with unilateral sixth nerve palsy, mean esotropia in primary position before surgery was 46.7 prism-diopters (PD) (95% CI 35.9-57.4 PD) and improved to 14.6 PD after surgery (95% CI 6.4-22.7 PD). The angle of deviation was significantly reduced by an average of 32.1 PD (p < 0.001, paired t-test; 95% CI 22.6-41.6 PD). Over all, 10 patients (55.6%) had a well-controlled esophoria with a postoperative alignment of within 10 PD of orthophoria without diplopia in the primary position, for distance and near. A further six patients (28.6%) required additional medial rectus recessions to achieve success. The only complication observed was slippage of the inferior rectus in one patient (4.2%), who consequently required further surgery. CONCLUSION: Botulinum toxin infiltration of the medial rectus in vertical rectus transposition surgery may be unnecessary, incurring cost, additional attendances and interventions for patients. Less than a third of all patients in our series required additional medial rectus recession later.