Efficacy of a Cationic Emulsion of Cyclosporine in Moderate Vernal Keratoconjunctivitis.

PURPOSE: The aim of this study was to demonstrate the efficacy of cyclosporine A 0.1% cationic emulsion (CsA CE) eye drops 4 times a day in pediatric patients affected by a moderate form of vernal keratoconjunctivitis (VKC). METHODS: This was a prospective study of pediatric patients, aged 5-16 years, with an active moderate form of VKC who were poor responders to topical antihistamines treatment and were treated 4 times a day with CsA CE. The clinical signs were graded for analysis as follows: hyperemia, tarsal papillae, and limbal papillae. RESULTS: Twenty-eight patients (22 males and 6 females) with a minimum follow-up period of 3 months were included in the analysis. Statistical analysis excluded tarsal papillae because of the very low baseline value. The clinical score of hyperemia and limbal papillae improved from the first evaluation and was maintained over the follow-up. No side effects were noted. CONCLUSION: CsA CE has been proposed as a treatment for severe forms of VKC. This study has shown that administration 4 times a day is also effective in the treatment of moderate forms of VKC in children.

Glaucoma Progression Diagnosis: The Agreement between Clinical Judgment and Statistical Software.

Background: To explore the agreement between clinical judgment and Guided Progression Analysis II (GPAII) in the evaluation of visual fields (VF) progression in patients with glaucoma. Methods: Three glaucoma experts and three general ophthalmologists were asked to rate the VF series by classifying them as progressive through the observation of the overview report. The agreement between clinical judgment and GPAII event analysis (EA) and trend analysis (TA) was assessed by Cohen statistic. The sensitivity and specificity of clinical judgment in detecting the presence of progression was evaluated considering the results of GPAII as the reference standard. Results: 66 VF series were included in the study. Glaucoma experts, general ophthalmologists, GPAII EA, and GPAII TA found progression in 39%, 38%, 15%, and 21% of the VF series (p < 0.05). The clinical judgment of glaucoma experts and general ophthalmologists was discordant with GPAII EA in 27.2% and 28.7% (k = 0.35, 95% CI 0.15−0.56 and k = 0.30, 95% CI 0.09−0.52) and with GPAII TA in 21.2% and 25.7% of the VF series examined (k = 0.51, 95% CI 0.31−0.72 and k = 0.41, 95% CI 0.18−0.62). Considering the GPAII EA and TA as reference standard, glaucoma experts showed a sensitivity of 90% and 92.8% and a specificity of 69.6% and 75%, while general ophthalmologists showed a sensitivity of 80% and 78.5% and a specificity of 69.6% and 73%. Conclusions: The agreement between clinical judgment and GPAII ranges from fair to moderate. Glaucoma experts showed better ability than general ophthalmologists in detecting VF progression.

Impact of screen exposure on pediatric vernal Keratoconjunctivitis: a survey during the COVID-19 pandemic in Italy.

BACKGROUND: The SARS-CoV-2 outbreak pushed the Italian government to start a strict lockdown, replacing school attendance with long-distance learning. This caused reduced exposure to sunlight but increased exposure to screens. Vernal keratoconjunctivitis (VKC) is a chronic inflammatory ocular condition in which exposure to light plays a cardinal role. We conducted an online survey to evaluate the impact of screen exposure on children with VKC during the COVID-19 lockdown. METHODS: We performed a survey-based observational study, asking patients followed at the Allergology clinics of Meyer Children's University Hospital in Florence and of Policlinico Umberto I in Rome to provide grading on 6 subjective ocular clinical manifestations presented during the lockdown and to give an estimate of their hours/day of screen exposure. RESULTS: Mean scores of signs and symptoms increased homogeneously when studying patients exposed to longer screen time. When comparing scores collected in 2019 to those in 2020, there was not a significant reduction in clinical manifestations, although the situation differed between the two centers due to geographical differences in sunlight exposure. CONCLUSION: During the lockdown, there was a reduction in sunlight exposure but conversely an increase in the time spent in front of screens that correlated with the worsening of VKC signs and symptoms in direct proportion to the hours/day of screen exposure. Our results also showed a statistically significant difference in the relative impact of long-distance learning on VKC clinical manifestations in the different Italian regions.

Long-Term Safety and Efficacy of Tacrolimus 0.1% in Severe Pediatric Vernal Keratoconjunctivitis.

PURPOSE: The aim of this study was to evaluate the safety and efficacy of tacrolimus 0.1% eye drops in a large population of pediatric patients affected by a severe form of vernal keratoconjunctivitis (VKC) who responded poorly to cyclosporine eye drops. METHODS: This is a retrospective study based on standardized clinical charts and data collection of consecutive patients affected by severe VKC who responded poorly to cyclosporine eye drops topical treatment but treated with tacrolimus 0.1% eye drops with a follow-up of 18 months. Four clinical signs were graded for analysis: hyperemia, tarsal papillae, giant papillae, and limbal papillae. The blood tests for kidney and liver function and the tacrolimus level were studied. Visits were scheduled at baseline and at 3, 6, 12, and 18 months. Patients received tacrolimus 0.1% eye drops in both eyes 2 times daily. RESULTS: Four hundred thirty-one patients were included. Three hundred twenty-five patients were affected by a seasonal form, whereas the remaining 106 by a perennial form. Statistical analysis on each single score showed a positive relevance (P < 0.001) from baseline to all other visits. No local or systemic complications were recorded. CONCLUSIONS: Tacrolimus has been proposed as a treatment for severe forms of VKC. This study has confirmed the safety and efficacy of tacrolimus 0.1% eye drops in a large pediatric population of patients affected by a severe form of VKC who responded poorly to cyclosporine eye drops.

The role of cognitive reserve in the relationship between metabolic syndrome and cognitive functioning.

Metabolic syndrome (MetS) is a cluster of vascular risk factors that can impact cognition. Cognitive reserve (CR), specifically early operators of reserve (e.g., education), have not been explored in the relationship between MetS and cognition. Adults 45-90 years old (n = 149) underwent neuropsychological testing and evaluation for MetS. Exploratory and confirmatory factor analyses defined neuropsychological domains and created a CR score based on early operators of CR. Regression analyses examined the association among MetS, CR, and neuropsychological performance. CFA revealed two neuropsychological factors: Episodic Memory and Executive Functioning. Controlling for age and physical ability, MetS and CR were significant predictors of the Factors. With CR in the model, MetS became a non-significant predictor of Executive Functioning; CR and physical ability were the most significant predictors. CR and MetS significantly predicted Episodic Memory . The results are discussed in the context of neuroprotective factors and cognitive aging.

Effects of listening to music in digestive endoscopy: A prospective intervention study led by nursing.

AIMS: To explore whether music can reduce anxiety and pain in patients who underwent diagnostic endoscopic examinations in conscious and deep sedation and to assess degree of satisfaction and willingness to repeat the procedure. DESIGN: Prospective study led by nursing. METHODS: Between March 2019-June 2019, consecutive outpatients undergoing endoscopic examinations were simple matched into four groups: Group 1: conscious sedation with music; Group 2: conscious sedation without music; Group 3: deep sedation with music and Group 4: deep sedation without music. Ten minutes before the procedure, two trainee nurses applied music. State-Trait Anxiety Inventory was used to evaluate anxiety. RESULTS: Before and at the end of the procedure, patients who listened to music had a lower level anxiety than those who did not listen and, also, reported lower pain intensity during procedure. Only within Group 1 median anxiety, measured after the procedure, is lower than that measured before. In the bivariate logistic regression model, pain and listening to music were independent factors for satisfaction and willingness to repeat procedure. CONCLUSION: music in digestive endoscopy reduce pain and anxiety in conscious sedation, thus could be used to reduce anxiety in support to conscious sedation leading to lower usage of deep sedation and consequently reduction of costs and adverse events. IMPACT: Anxiety in digestive endoscopy limits patients' satisfaction. Music in digestive endoscopy as a specific nursing intervention could reduce anxiety of patients. This nursing intervention study confirms positive effect of music in digestive endoscopy. As part of nursing management, the addition of music to daily care practice in digestive endoscopy may reduce anxiety and increase the patient's degree of satisfaction. Use of music could limit deep sedation use in digestive endoscopy with consequent reduction of risks for patients, execution times, and costs of procedures.

Nursing issues in enteral nutrition during prone position in critically ill patients: A systematic review of the literature.

BACKGROUND: Early enteral nutrition (EN) and prone position may both improve the outcome of patients affected by moderate to severe Acute Respiratory Distress Syndrome. Recent guidelines suggest to administer early EN also during prone position. However, EN intolerance, such as high residual gastric volumes, regurgitation or vomiting, may occur during pronation. AIM: This systematic review aims to assess the occurrence of high residual gastric volume, regurgitation or vomiting episodes, that can be encountered in patients receiving EN during prone position. METHODS: We have conducted a systematic review. We queried three scientific databases (MEDLINE, EMBASE and CINAHL) from inception until November 19, 2019 without language restrictions, using keywords and related MeSH terms. All relevant articles enrolling adult patients receiving invasive mechanical ventilation and evaluating the use of early EN during prone position were included. RESULTS: From 111 records obtained, we included six studies. All studies but one reported no differences with respect to gastric residual volumes between supine and prone positions. A 24-hours EN administration protocol seems to be better, as compared to an 18-hours feeding protocol. The need to stop EN and vomiting episodes were higher during prone position, although the rate of high gastric volume was similar between supine and prone positions. Ventilator associated pneumonia, lengths of stay and mortalities were similar between supine and prone positions. Only one study reported lower mortality in patients receiving EN throughout the entire day, as compared to an 18-hours administration protocol. CONCLUSION: Protocols should be followed by healthcare providers in order to increase the enteral feeding volume, while avoiding EN intolerance (such as EN stops, high residual volume, regurgitation and vomiting).

Evaluating the Influence of Social Engagement on Cognitive Impairment and Mobility Outcomes Within the Boston RISE Cohort Study.

OBJECTIVE: We investigated the associations between mild cognitive impairment (MCI), social engagement (SE), and mobility. DESIGN: We evaluated data from a cohort study of older adult primary care patients (N = 430). Outcomes included self-reported function (Late-Life Function Instrument [LLFI]) and performance-based mobility (Short Physical Performance Battery score [SPPB]). Linear regression models evaluated the association between MCI and mobility, MCI and SE, mobility measures and SE, and whether SE mediated the association between MCI status and mobility. RESULTS: Participants with MCI had significantly lower mobility and lower SE as compared with those without MCI (LLFI: 53.5 vs. 56.9, P < 0.001; SPPB: 7.9 vs. 9.3, P < 0.001; SE score: 44.9 vs. 49.0, P < 0.001). Mild cognitive impairment was significantly associated with both LLFI and SPPB (LLFI ß = -2.93, P < 0.001; SPPB ß = -1.26, P < 0.001) and SE (ß = -3.20, P < 0.001). Social engagement was significantly associated with both LLFI and SPPB (LLFI ß = 0.22; P < 0.001; SPPB ß = 0.08; P < 0.001). There was a positive association between SE and mobility (P< 0.05). A mediator effect of SE was supported when evaluating the association between MCI and mobility. CONCLUSIONS: Among older adult primary care patients at risk for mobility decline, higher levels of SE mitigate the association between MCI and mobility.

The Association Between Social Engagement, Mild Cognitive Impairment, and Falls Among Older Primary Care Patients.

OBJECTIVES: To examine associations between mild cognitive impairment (MCI) and falls among primary care patients, and to investigate whether social engagement (SE) modifies these associations. DESIGN: Cross sectional analysis using baseline data from an observational cohort study. SETTING: Primary care. PARTICIPANTS: Community-dwelling older adults (N=430) at risk of mobility decline with a mean age of 76.6 years (range 65-96y). MAIN OUTCOME MEASURES: The number of falls in the past year was reported at the baseline interview. MCI was identified using a cutoff of 1.5 SD below the age-adjusted mean on at least 2 of the standardized cognitive performance tests. SE (eg, keeping in touch with friends and family, volunteering, participating social activities…) was assessed with the Late Life Function and Disability Instrument, and required a score above the median value 49.5 out of 100. RESULTS: MCI was present among 42% of participants and 42% reported at least 1 fall in the preceding year. Using generalized estimating equations, MCI was associated with a 77% greater rate of falls (P<.05). There was a statistically significant interaction between SE and MCI on the rate of falls (P<.01), such that at a high level of SE, MCI was not statistically associated with falls (P=.83). In participants with lower levels of SE, MCI is associated with 1.3 times greater rate of falls (P<.01). CONCLUSIONS: While MCI is associated with a greater risk for falls, higher levels of SE may play a protective role.

The Relationship Between Cognitive Impairment and Upper Extremity Function in Older Primary Care Patients.

BACKGROUND: Individuals with mild cognitive impairment (MCI), often a precursor to dementia, experience limitations in completing daily activities. These limitations are particularly important to understand, as they predict risk for dementia. Relations between functional changes and both cognitive decline and upper extremity motor impairments have been reported, but the contribution of motor function to relations between cognitive function and functional independence remains poorly understood. We examined the relationship between cognition and upper extremity activities, and whether this relation was mediated by motor function. METHODS: A total of 430 community-dwelling primary care patients aged at least 65 years from the Boston Rehabilitative Impairment Study of the Elderly completed self-report measures of upper extremity function, tests of neuromuscular attributes to measure motor function (reaction time, pronosupination of the hands), and neuropsychological measures. Participants were classified based on cognitive performance into groups: MCI and without MCI, with MCI further classified by cognitive subtype. Regression and mediation analyses examined group differences and relations between cognitive function, upper extremity function, and neuromuscular attributes. RESULTS: MCI participants demonstrated poorer neuromuscular attributes and self-reported upper extremity function, and neuromuscular attributes significantly mediated positive relations between cognitive status and self-reported upper extremity function. Poorer self-reported upper extremity function was most prominent for groups with executive dysfunction. CONCLUSIONS: Together with previous research, results suggest that the relationship between cognitive function, motor function, and functional activities is not confined to mobility tasks but universally related to body systems and functional activities. These findings inform new approaches for dementia risk screening and rehabilitative care.

Chronic Pain and Attention in Older Community-Dwelling Adults.

OBJECTIVES: To examine the cross-sectional relationship between chronic pain and complex attention in a population of community-living older adults. DESIGN: Prospective cross-sectional cohort study. SETTING: Population-based Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly of Boston Study II. PARTICIPANTS: Individuals aged 71 to 101 (N=354). MEASUREMENTS: Chronic pain was measured using the pain severity and interference subscales of the Brief Pain Inventory. Four subscales of the Test of Everyday Attention were used to measure domains of attention switching and selective, sustained, and divided attention. RESULTS: Before and after multivariable adjustment, pain severity was associated with poorer scores on measures of selective and sustained attention. Pain interference scores also were significantly inversely associated with selective attention. CONCLUSION: Chronic pain is associated with poorer performance in selective and sustained attention in community-dwelling older adults. Further research is needed to determine whether effective pain management could lead to better attentional performance in older adults. Older adults who live with chronic pain, often undertreated, are potentially at risk of cognitive difficulties and related functional consequences.

Prevalence of Cognitive Impairment and Association With Survival Among Older Patients With Hematologic Cancers.

Importance: As the population ages, cognitive impairment has promised to become increasingly common among patients with cancer. Little is known about how specific domains of cognitive impairment may be associated with survival among older patients with hematologic cancers. Objective: To determine the prevalence of domain-specific cognitive impairment and its association with overall survival among older patients with blood cancer. Design, Setting, and Participants: This prospective observational cohort study included all patients 75 years and older who presented for initial consultation in the leukemia, myeloma, or lymphoma clinics of a large tertiary hospital in Boston, Massachusetts, from February 1, 2015, to March 31, 2017. Patients underwent screening for frailty and cognitive dysfunction and were followed up for survival. Exposures: The Clock-in-the-Box (CIB) test was used to screen for executive dysfunction. A 5-word delayed recall test was used to screen for impairment in working memory. The Fried frailty phenotype and Rockwood cumulative deficit model of frailty were also assessed to characterize participants as robust, prefrail, or frail. Results: Among 420 consecutive patients approached, 360 (85.7%) agreed to undergo frailty assessment (232 men [64.4%] and 128 women [35.6%]; mean [SD] age, 79.8 [3.9] years), and 341 of those (94.7%) completed both cognitive screening tests. One hundred twenty-seven patients (35.3%) had probable executive dysfunction on the CIB, and 62 (17.2%) had probable impairment in working memory on the 5-word delayed recall. Impairment in either domain was modestly correlated with the Fried frailty phenotype (CIB, ρ = 0.177; delayed recall, ρ = 0.170; P = .01 for both), and many phenotypically robust patients also had probable cognitive impairment (24 of 104 [23.1%] on CIB and 9 of 104 [8.7%] on delayed recall). Patients with impaired working memory had worse median survival (10.9 [SD, 12.9] vs 12.2 [SD, 14.7] months; log-rank P < .001), including when stratified by indolent cancer (log-rank P = .01) and aggressive cancer (P < .001) and in multivariate analysis when adjusting for age, comorbidities, and disease aggressiveness (odds ratio, 0.26; 95% CI, 0.13-0.50). Impaired working memory was also associated with worse survival for those undergoing intensive treatment (log-rank P < .001). Executive dysfunction was associated with worse survival only among patients who underwent intensive treatment (log-rank P = .03). Conclusions and Relevance: These data suggest that domains of cognitive dysfunction may be prevalent in older patients with blood cancer and may have differential predictive value for survival. Targeted interventions are needed for this vulnerable patient population.

Verbal Memory Deficits in OEF/OIF/OND Veterans Exposed to Blasts at Close Range.

OBJECTIVES: This study investigated the relationship between close proximity to detonated blast munitions and cognitive functioning in OEF/OIF/OND Veterans. METHODS: A total of 333 participants completed a comprehensive evaluation that included assessment of neuropsychological functions, psychiatric diagnoses and history of military and non-military brain injury. Participants were assigned to a Close-Range Blast Exposure (CBE) or Non-Close-Range Blast Exposure (nonCBE) group based on whether they had reported being exposed to at least one blast within 10 meters. RESULTS: Groups were compared on principal component scores representing the domains of memory, verbal fluency, and complex attention (empirically derived from a battery of standardized cognitive tests), after adjusting for age, education, PTSD diagnosis, sleep quality, substance abuse disorder, and pain. The CBE group showed poorer performance on the memory component. Rates of clinical impairment were significantly higher in the CBE group on select CVLT-II indices. Exploratory analyses examined the effects of concussion and multiple blasts on test performance and revealed that number of lifetime concussions did not contribute to memory performance. However, accumulating blast exposures at distances greater than 10 meters did contribute to poorer performance. CONCLUSIONS: Close proximity to detonated blast munitions may impact memory, and Veterans exposed to close-range blast are more likely to demonstrate clinically meaningful deficits. These findings were observed after statistically adjusting for comorbid factors. Results suggest that proximity to blast should be considered when assessing for memory deficits in returning Veterans. Comorbid psychiatric factors may not entirely account for cognitive difficulties. (JINS, 2018, 24, 466-475).

Elevated rates of memory impairment in military service-members and veterans with posttraumatic stress disorder.

INTRODUCTION: Studies investigating the neurocognitive effects of posttraumatic stress disorder (PTSD) routinely find "deficits" in various cognitive domains. However, the rate of cognitive impairment in individuals with PTSD remains unclear, as studies have focused on null hypothesis testing (NHT) and inferring patterns of impairment rather than empirically determining the rate of cognitive impairment in this sample. METHOD: This study examined rates of cognitive impairment using a domain-specific approach in non-treatment-seeking Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn service members and veterans with (n = 92) and without (n = 79) PTSD and without substance abuse/dependence who passed a performance validity measure and were matched on age, education, estimated IQ, and ethnicity. Chi-square analyses were used to compare the rate of cognitive impairment across groups based on normative scores using three cutoffs (-1, -1.5, and -2 SDs). NHT was also used to compare performances across groups. RESULTS: Individuals with PTSD showed higher rates of impairment in memory (-1-SD cutoff) than controls, but equivalent rates of impairment in attention, processing speed, and executive functioning; no significant differences were found on NHT. Impairment in any domain was also more prevalent in PTSD (-1-, -1.5-, and -2-SD cutoffs). No differences were found on NHT or rates of impairment in individuals with PTSD with (n = 34) and without (n = 58) depression. CONCLUSIONS: Patients with PTSD were more likely to meet criteria for memory impairment and to show impairment in any domain than controls. Patients with PTSD and comorbid depression were no more likely to be impaired in any cognitive domain or to have lower scores on individual cognitive tasks than patients with PTSD alone. Clinicians noting cognitive impairment in individuals with PTSD should exercise caution before ascribing that impairment to another etiology if deficits are limited to memory.

The Clock-in-the-Box, a brief cognitive screen, is associated with failure to return home in an elderly hospitalized sample.

PURPOSE: Cognitive screening upon hospital admission can provide important information about the patient's ability to process information during the inpatient stay. The Clock-in-the-Box (CIB) is a rapidly administered cognitive screening measure which has been previously validated with cognitive screening and neuropsychological assessments. The purpose of this study is to demonstrate the predictive validity of the CIB for discharge location among a sample of older medical inpatients. PATIENTS AND METHODS: Hospitalized Veterans (N=218), aged 55 years and older, were recruited on the day after admission after they gave their consent. These participants completed the CIB, the Montreal Cognitive Assessment, and self-report measures of daily functioning. Using logistic regression models, the bivariable and multivariable impact of the cognitive screening and functional assessments were examined for their ability to predict whether the participants did not return home after hospitalization (eg, admission to subacute rehabilitation facilities or nursing facilities). RESULTS: The participants were older (mean 71.5±9.5 years) and predominantly male (92.7%). The CIB score was independently associated with discharge to locations other than home (odds ratio =0.72, 95% confidence interval =0.60-0.87, P=0.001) and remained associated after adjusting for demographics, prehospitalization functional abilities, and Montreal Cognitive Assessment score (adjusted odds ratio =0.55, 95% confidence interval =0.36-0.83, P=0.004). CONCLUSION: The current evidence, combined with its brevity and ease of use, supports the use of the CIB as a cognitive screen for inpatient older adults, in order to help inform clinical treatment decisions and discharge planning.

Luminescence and Nonlinear Optical Properties in Copper(I) Halide Extended Networks.

The syntheses, structures, and luminescence properties of a series of copper(I) halide coordination polymers, prepared with mono- and bidentate N-heteroaromatic ligands, are reported. These metal-organic coordination networks form [Cu2I2L]n for bidentate ligands (where L = pyrazine (1), quinazoline (2)) and [CuIL]n for monodentate ligands (where L = 3-benzoylpyridine (3) and 4-benzoylpyridine(4)). Both sets of compounds exhibit a double-stranded stair-Cu2I2-polymer, or "ladder" structure with the ligand coordinating to the metal in a bidentate (bridging two stairs) or monodentate mode. The copper bromide analogues for the bidentate ligands were also targeted, [Cu2Br2L]n for L = pyrazine (5) with the same stair structure, as well as compositions of [CuBr(L)]n for L = pyrazine (6) and quinazoline (7), which have a different structure type, where the -Cu-Br- forms a single-stranded "zigzag" chain. These copper halide polymers were found to be luminescent at room temperature, with emission peaks ranging from ∼550 to 680 nm with small shifts at low temperature. The structure (stair or chain), the halide (I or Br), as well as the ligand play an important role in determining the position and intensity of emission. Lifetime measurements at room and low temperatures confirm the presence of thermally activated delayed fluorescence, or singlet harvesting for compounds 1, 2, and 7. We also investigated the nonlinear optical properties and found that, of this series, [CuBr(quinazoline)]n shows a very strong second harmonic generating response that is ∼150 times greater than that of α-SiO2.

Whole-Genome Characterization and Strain Comparison of VT2f-Producing Escherichia coli Causing Hemolytic Uremic Syndrome.

Verotoxigenic Escherichia coli infections in humans cause disease ranging from uncomplicated intestinal illnesses to bloody diarrhea and systemic sequelae, such as hemolytic uremic syndrome (HUS). Previous research indicated that pigeons may be a reservoir for a population of verotoxigenic E. coli producing the VT2f variant. We used whole-genome sequencing to characterize a set of VT2f-producing E. coli strains from human patients with diarrhea or HUS and from healthy pigeons. We describe a phage conveying the vtx2f genes and provide evidence that the strains causing milder diarrheal disease may be transmitted to humans from pigeons. The strains causing HUS could derive from VT2f phage acquisition by E. coli strains with a virulence genes asset resembling that of typical HUS-associated verotoxigenic E. coli.

Effects of Megaplasmid Loss on Growth of Neurotoxigenic Clostridium butyricum Strains and Botulinum Neurotoxin Type E Expression.

Clostridium butyricum strains that atypically produce the botulinum neurotoxin type E (BoNT/E) possess a megaplasmid of unknown functions in their genome. In this study, we cured two botulinum neurotoxigenic C. butyricum type E strains of their megaplasmids, and compared the obtained megaplasmid-cured strains to their respective wild-type parental strains. Our results showed that the megaplasmids do not confer beta-lactam resistance on the neurotoxigenic C. butyricum type E strains, although they carry several putative beta-lactamase genes. Instead, we found that the megaplasmids are essential for growth of the neurotoxigenic C. butyricum type E strains at the relatively low temperature of 15°C, and are also relevant for growth of strains under limiting pH and salinity conditions, as well as under favorable environmental conditions. Moreover, the presence of the megaplasmids was associated with increased transcript levels of the gene encoding BoNT/E in the C. butyricum type E strains, indicating that the megaplasmids likely contain transcriptional regulators. However, the levels of BoNT/E in the supernatants of the cured and uncured strains were similar after 24 and 48 h culture, suggesting that expression of BoNT/E in the C. butyricum type E strains is not ultimately controlled by the megaplasmids. Together, our results reveal that the C. butyricum type E megaplasmids exert pleiotropic effects on the growth of their microbial hosts under optimal and limiting environmental conditions, and also highlight the possibility of original regulatory mechanisms controlling the expression of BoNT/E.

Effect of Pain and Mild Cognitive Impairment on Mobility.

OBJECTIVES: To examine the effect of pain and mild cognitive impairment (MCI)-together and separately-on performance-based and self-reported mobility outcomes in older adults in primary care with mild to moderate self-reported mobility limitations. DESIGN: Cross-sectional analysis. SETTING: Academic community outpatient clinic. PARTICIPANTS: Individuals aged 65 and older in primary care enrolled in the Boston Rehabilitative Impairment Study in the Elderly who were at risk of mobility decline (N=430). MEASUREMENTS: Participants with an average score greater than three on the Brief Pain Inventory (BPI) were defined as having pain. MCI was defined using age-adjusted scores on a neuropsychological battery. Multivariable linear regression models assessed associations between pain and MCI, together and separately, and mobility performance (habitual gait speed, Short Physical Performance Battery), and self-reports of function and disability in various day-to-day activities (Late Life Function and Disability Instrument). RESULTS: The prevalence of pain was 34% and of MCI was 42%; 17% had pain only, 25% had MCI only, 17% had pain and MCI, and 41% had neither. Participants with pain and MCI performed significantly worse than all others on all mobility outcomes (P<.001). Participants with MCI only or pain only also performed significantly worse on all mobility outcomes than those with neither (P<.001). CONCLUSION: Mild to moderate pain and MCI were independently associated with poor mobility, and the presence of both comorbidities was associated with the poorest status. Primary care practitioners who encounter older adults in need of mobility rehabilitation should consider screening them for pain and MCI to better inform subsequent therapeutic interventions.

Event-based prospective memory among veterans: The role of posttraumatic stress disorder symptom severity in executing intentions.

OBJECTIVE: Posttraumatic stress disorder (PTSD) has been linked with neuropsychological deficits in several areas, including attention, learning and memory, and cognitive inhibition. Although memory dysfunction is among the most commonly documented deficits associated with PTSD, our existing knowledge pertains only to retrospective memory. The current study investigated the relationship between PTSD symptom severity and event-based prospective memory (PM). METHOD: Forty veterans completed a computerized event-based PM task, a self-report measure of PTSD, and measures of retrospective memory. RESULTS: Hierarchical regression analysis results revealed that PTSD symptom severity accounted for 16% of the variance in PM performance, F(3, 36) = 3.47, p < .05, after controlling for age and retrospective memory. Additionally, each of the three PTSD symptom clusters was related, to varying degrees, with PM performance. CONCLUSIONS: Results suggest that elevated PTSD symptoms may be associated with more difficulties completing tasks requiring PM. Further examination of PM in PTSD is warranted, especially in regard to its impact on everyday functioning.