Two waves of distinct hematopoietic progenitor cells colonize the fetal thymus.

The generation of T cells depends on the migration of hematopoietic progenitor cells to the thymus throughout life. The identity of the thymus-settling progenitor cells has been a matter of considerable debate. Here we found that thymopoiesis was initiated by a first wave of T cell lineage-restricted progenitor cells with limited capacity for population expansion but accelerated differentiation into mature T cells. They gave rise to αß and γδ T cells that constituted Vγ3(+) dendritic epithelial T cells. Thymopoiesis was subsequently maintained by less-differentiated progenitor cells that retained the potential to develop into B cells and myeloid cells. In that second wave, which started before birth, progenitor cells had high proliferative capacity but delayed differentiation capacity and no longer gave rise to embryonic γδ T cells. Our work reconciles conflicting hypotheses on the nature of thymus-settling progenitor cells.

Glucocorticoid Sensitivity Among Young Survivors of Childhood Acute Lymphoblastic Leukemia: What Does It Matter?

The aim of the study was to assess glucocorticoid sensitivity in survivors of childhood acute lymphoblastic leukemia using in vivo and in vitro tests. Thirty leukemia survivors of both sexes aged ≥18 years participated in the study and at least two years after therapy withdrawal. In vivo tests comprised: a) a very low dose intravenous dexamethasone suppression test for measurement of serum cortisol before, after, and % suppression, compared with 32 age-matched controls; and b) 0.25 mg overnight oral dexamethasone suppression test for assessment of salivary cortisol before, after, and % suppression. In vitro methods comprised: c) glucocorticoid receptor polymorphisms: BcI1-NR3C1 and A3669G; and d) splicing variant of glucocorticoid receptor GR-α mRNA by real-time quantitative polymerase chain reaction, compared with 32 controls. There was a reduction in salivary cortisol, and 73.3% of leukemia survivors showed high sensitivity according to % suppression after oral dexamethasone (p<0.05). Serum cortisol at baseline, after the test, % suppression after intravenous dexamethasone, and the percentage of high sensitivity were reduced in the leukemia group (%F=36.7; p<0.05). The BcI1-NR3C1 and A3669G polymorphisms were present in 11/30 (36.7%) and 5/30 (16.7%) patients, respectively. GR-α mRNA levels were lower in the leukemia group than in the controls (p<0.05). Survivors of acute lymphoblastic leukemia presented with reduced glucocorticoid sensitivity. Glucocorticoid sensitivity allows individualized treatment to avoid adverse effects and may be involved in cardiovascular disease risk among this particular group of cancer survivors.

Self-Assembly and Antimicrobial Activity of Lipopeptides Containing Lysine-Rich Tripeptides.

The conformation and self-assembly of two pairs of model lipidated tripeptides in aqueous solution are probed using a combination of spectroscopic methods along with cryogenic-transmission electron microscopy (cryo-TEM) and small-angle X-ray scattering (SAXS). The palmitoylated lipopeptides comprise C16-YKK or C16-WKK (with two l-lysine residues) or their respective derivatives containing d-lysine (k), i.e., C16-Ykk and C16-Wkk. All four molecules self-assemble into spherical micelles which show structure factor effects in SAXS profiles due to intermicellar packing in aqueous solution. Consistent with micellar structures, the tripeptides in the coronas have a largely unordered conformation, as probed using spectroscopic methods. The molecules are found to have good cytocompatibility with fibroblasts at sufficiently low concentrations, although some loss of cell viability is noted at the highest concentrations examined (above the critical aggregation concentration of the lipopeptides, determined from fluorescence dye probe measurements). Preliminary tests also showed antimicrobial activity against both Gram-negative and Gram-positive bacteria.

Antillean manatee (Trichechus manatus manatus Linnaeus, 1758) Tongue Morphology and Adaptive Herbivorous Implications.

Morphological study of the tongue is an interesting way of understanding evolutionary processes associated with feeding habits. Therefore, the aim of the present study was to describe the tongue morphology of the Antillean manatee and to understand possible morphological relationships with its way of capturing food. Macroscopic dissections and light and scanning electron microscopy analyses of seven manatee tongues were performed. The tongue in Antillean manatees is a muscular and robust organ, divided into apex, body, and root. It is firmly adhered to the floor of the oral cavity. Lingual papillae were distributed over the entire tongue surface. They were identified as filiform papillae concentrated in the apex. Fungiform papillae were present on the apex and lateral regions. Foliate papillae were located on the dorsolateral portion of the root. Lentiform papillae were located across the dorsal tongue surface. The mucosa was lined by a keratinized stratified squamous epithelium presenting compound tubuloacinar glands and taste buds in the foliate papillae. The tongue of the Antillean manatee is similar to other Sirenia species, both of which share a completely herbivorous diet.

Measurement properties of patient-reported outcome measures for women with dysmenorrhea: A systematic review.

BACKGROUND: Dysmenorrhea, or menstrual pain, is a subjective experience, and can only be assessed by patient-reported outcomes. These instruments should be reliable, valid and responsive. AIM: To identify and critically appraise the available evidence for the measurement properties of specific patient-reported outcome measures used for dysmenorrhea. METHODS: The PRISMA statement was used to report this systematic review. Databases searched were PubMed, SCOPUS, CINAHL, Web of Science, ScienceDirect and Google Scholar (April 2021; updated on February 2023). Original studies with primary data collection, with no restriction on language and publication date that reported psychometric properties of one or more dysmenorrhea-related patient-reported outcome measure. The literature searches, selection of studies, data extraction and assessment of the risk of bias were performed independently by two reviewers and followed the COSMIN guidelines. RESULTS: Thirty studies were analysed in this review, and 19 patient-reported outcome measures were evaluated. The instruments varied in relation to the measured construct and measurement properties (validity, reliability and responsiveness). The methodological quality of the studies and the quality of evidence of the patient-reported outcome measures were variable. Among the 13 studies that reported the development of patient-reported outcome measures, most had inadequate methodological quality, and the overall rating was insufficient or inconsistent. CONCLUSIONS: The Dysmenorrhea Symptom Interference (DSI) scale was the only identified patient-reported outcome measure that has the potential to be recommended because of its sufficient rating combined with moderate quality of evidence for content validity. Future studies should further evaluate the measurement properties of the existing patient-reported outcome measures, or develop new patient-reported outcome measures following the COSMIN methodology. PATIENT OR PUBLIC CONTRIBUTION: Not applicable as this is a systematic review. TRIAL REGISTRATION: PROSPERO protocol: CRD42021244410. Registration on April 22, 2021.

Neural binocular summation and the effect of defocus on the pattern electroretinogram and visual evoked potentials for different pupil sizes.

PURPOSE: To evaluate the influence of defocus and pupil size on subjective (visual acuity [VA]) and objective (electrophysiology) descriptors of human vision and their effect on binocular visual performance by means of neural binocular summation (BS). METHODS: Fifteen healthy young subjects were recruited in this crossover study. Pattern electroretinogram (PERG) and visual evoked potentials (VEP) were measured under two levels of positive (+1.5 and +3.0 D) spherical and astigmatic defocus (axis 90°). Pupil size was controlled to reduce the inter-individual variability factor. RESULTS: Low- and high-contrast VA showed poorer visual performance in the monocular versus the binocular condition. Positive BS (for VA) was higher with greater pupil size and higher levels of defocus. In the visual electrophysiology tests (i.e., VEP and PERG), peak time and amplitude were affected by pupil size and defocus. The increase in peak time was larger and the reduction in amplitude was more significant with greater levels of defocus and smaller pupil sizes. For the VEP, positive BS was found in all conditions, being stronger with larger amounts of defocus and pupil size (for the P100 amplitude). Significant negative correlations were observed between the P100 amplitude and VA BSs. CONCLUSION: Smaller pupil size and levels of defocus produced greater changes in cortical activity as evidenced by both the PERG and VEP. Considering these changes and the obtained positive BS, the mechanism could be initiated as early as the retinal processing stage, then being modulated and enhanced along the visual pathway and within the visual cortex.

The role of the pharmacist in the hospital discharge of cancer patients: an integrative review.

INTRODUCTION: Patients with cancer need care from a multidisciplinary team due to the complexity of the clinical picture and proposed treatment. Hospital discharge is a critical step, because pharmacotherapy changes may occur during hospitalization, leading to potential medication-related problems at home. OBJECTIVE: To identify publications which describe the activities performed by the pharmacist at the hospital discharge of patients with cancer. METHOD: This is an integrative systematic literature review. A search was carried out in the MEDLINE databases, via Pubmed, Embase, and Virtual Health Library, using the following descriptors: "Patient Discharge", "Pharmacists", "Neoplasms." Studies that reported activities performed by the pharmacist at the hospital discharge of patients with cancer were included. RESULTS: Five hundred and two studies were identified, of which seven met the eligibility criteria. Most were conducted in the United States (n = 3), and the rest in Belgium, Brazil, Canada, and Italy. Among the services provided by the pharmacist at discharge, medication reconciliation was the most widely described. Other activities such as counseling, education, identification, and resolution of drug-related problems were also carried out. CONCLUSION: In the scenario of hospital discharge of patients with cancer, the participation of pharmacists is still to be seen as of significance in regards to publications. Despite this, the results suggest that the actions of this professional contribute to patient orientation and the safe use of prescription drugs for use at home.

Do the instruments used to assess fibromyalgia symptoms according to American College of Rheumatology criteria generate similar scores in other chronic musculoskeletal pain?

BACKGROUND: As with fibromyalgia, several musculoskeletal disorders are characterized by chronic pain, raising a clinical question - do the instruments used to assess fibromyalgia symptoms according to ACR criteria (ACR criteria) generate similar scores in other chronic musculoskeletal pain? OBJECTIVE: To compare the symptoms among fibromyalgia and other chronic musculoskeletal pain. Additionally, we also compared the most researched outcomes in fibromyalgia (i.e., present pain at rest and after movement; fatigue; pain severity and impact; function, global impact, and fibromyalgia symptom). METHODS: A cross-sectional study. Participants over 18 years old were included if they presented report of chronic musculoskeletal pain (≥ 3 months) and after that, they were divided into two groups (fibromyalgia and chronic pain). They answered the Fibromyalgia Impact Questionnaire-Revised (FIQ-R), Brief Pain Inventory (BPI), Numerical Pain Rating Scale (NPRS) for pain and fatigue, WPI, and SSS. RESULTS: A total of 166 participants were included in this study into two independent groups (chronic pain, n = 83; fibromyalgia, n = 83). We observed significant differences (p < 0.05) and large effect sizes (Cohen's d, ≥ 0.7) in clinical outcomes comparisons between groups (i.e., widespread pain; symptom severity; present pain at rest and after movement; fatigue; pain severity and impact; function, global impact, and fibromyalgia symptoms). CONCLUSION: Fibromyalgia patients (2016 ACR criteria) compared to other chronic musculoskeletal pain patients have higher levels of pain (at rest or after movement) and fatigue, greater impairment in both functionality and global impact, and worse symptoms. Therefore, the WPI and SSS instruments should be used exclusively to assess fibromyalgia symptoms.

Pupil size effect on binocular summation for visual acuity and light disturbance.

PURPOSE: Smaller pupil size under binocular conditions could justify partially the improvement of visual performance when compared to monocular conditions. The purpose of this study was to assess the binocular summation for increasing levels of spherical and cylindrical defocus when the pupil size factor is ruled out as a confounding factor. METHODS: Fifteen young subjects were recruited in this crossover study. Light disturbance index (LDI) was evaluated with the light disturbance analyzer and low (LCDVA) and high (HCDVA) contrast visual acuity with the ETDRS test. Two positive spherical and cylindrical defocus levels (+ 1.5 and + 3.0 D) were used to induce a controlled degradation of the retinal image for two pupil sizes (3 and 5 mm). RESULTS: Our results showed poorer visual performance in monocular than the binocular condition. An increasing deterioration was observed with the level of spherical defocus. Positive binocular summation for visual acuity was found in all the parameters studied and was stronger under larger pupil size and for higher levels of spherical defocus. It was observed a positive binocular summation for the LDI under all the conditions studied. Strong and significant correlations were found between LDI and LCDVA and between LDI and HCDVA for all the conditions. Higher correlations were obtained between disturbance index and visual acuity for spherical defocus compared to cylindrical. CONCLUSION: Binocular summation was observed under different conditions of spherical and cylindrical optical degradation of the image quality when the pupil size was fully controlled. This suggests that a neural factor is involved.

Short-term delay in neural response with multifocal contact lens might start at the retinal level.

INTRODUCTION: Multifocal simultaneous imaging challenges the visual system to process the multiple overlaps of focused and defocused images. Retinal image processing may be an important step in neuroadaptation to multifocal optical images. Our aims are, firstly to evaluate the short-term effect of different multifocal contact lenses (MF) on retinal activity in young healthy subjects (Experiment#1) and secondly, to evaluate any changes in retinal activity in presbyopic patients fitted with MF over a 15-day period (Experiment#2). METHODS: In Experiment-#1, 10 emmetropic healthy young subjects were included to evaluate the short-term effect of different MFs designs. In Experiment #2, 4 presbyopic subjects were included to wear MF for 15 days. Following the ISCEV Standards, multifocal electroretinograms (mfERGs) were recorded to evaluate different retinal regions under different conditions: with single vision contact lens (SVCL) and with center-distance and center-near MF. RESULTS: In Exp#1 the peak time of N1, P1 and N2 were found to be delayed with the MF (p ≤ 0.040). There was a significant reduction for N1 amplitude in all retinal regions (p < 0.001), while for P1 and N2 amplitudes this reduction was more significant in the peripheral regions (p < 0.005, ring 5 to 6). With center-near MF the mean response density (nV/deg2) showed a significant decrease in all wave components of the mfERGs response, particularly from Ring 3 to Ring 6 (p < 0.001, all Rings). In Exp#2, the mean mfERG response is similar between SVCL and center-distance MF, while center-near MF showed an increase in implicit time N1 and P1 on day 1 that tends to recover to baseline values after 15 days of MF wear. CONCLUSIONS: significant changes in the mfERGs responses were found with the MF lens, being most noticeable with the center-near MF lens design. The present results suggest that the observed delay in cortical response described during the adaptation to multifocality may partially begin at the retina level.

Implementation of a school-based physical activity intervention for Brazilian adolescents: a mixed-methods evaluation.

The effectiveness of physical activity interventions can be improved through examining the aspects related to their implementation. However, little such evidence has been collected, particularly in low- and middle-income countries. This study aimed to evaluate the implementation of a school-based physical activity intervention with qualitative and quantitative data from different actors (students, teachers and parents) involved in developing the program. The program was conducted in 2017 with three main components: (i) teacher training, (ii) environmental changes and (iii) educational actions. Mixed-method evaluation was performed by an independent evaluation team using a validated indicator matrix for the implementation process, including the self-reported information of students, teachers and parents, as well as interviews with teachers. In the 3 eligible schools, 350 adolescents (51% girls) answered the implementation questionnaire, as did 45 parents (84% mothers), and 47 teachers (70% female). In the qualitative analysis, 18 teachers participated. Categorical analysis found that the intervention was considered feasible by teachers. In general, teachers had a more positive perception of the implementation than did students. The lack of engagement from the school community and parents and the busy schedule of teachers were indicated to be the main difficulties. In conclusion, despite the teachers' motivation, some barriers prevented the successful implementation of the program.

THC shows activity against cultured Plasmodium falciparum.

The FDA approved drug Dronabinol was identified in a previous study applying virtual screening using the haemozoin crystal as a target against malaria parasites. The active ingredient of dronabinol is synthetic tetrahydrocannabinol (THC), which is one of the major cannabinoids from Cannabis sativa. Traditional use of cannabis for malaria fever was reported in the world's oldest pharmacopoeia, dating to around 5000 years ago. In this research we report that THC inhibits ß-haematin (synthetic haemozoin) and malaria parasite growth. Due the psychoactivity of THC, CBD, the other major naturally occurring cannabinoid that lacks the off-target psychoactive effects of THC, was also tested and inhibited ß-haematin but showed only a mild antimalarial activity. To evaluate whether THC inhibit haemozoin formation, we performed a cellular haem fractionation assay that indicated that is not the likely mechanism of action. For the first time, the cannabinoid chemical structure is raised as a new chemical class to be further studied for malaria treatment, aiming to overcome the undesirable psychoactive effects of THC and optimize the antimalarial effects.

SARS-CoV-2 in children with cancer in Brazil: Results of a multicenter national registry.

BACKGROUND: Strategies to mitigate the impact of COVID-19 in special populations are complex and challenging. Few studies have addressed the impact of COVID-19 on pediatric patients with cancer in low- and middle-income countries. METHODS: Multicenter observational cohort study with prospective records and retrospective analyses starting in April 2020 in 21 pediatric oncology centers distributed throughout Brazil. PARTICIPANTS: Patients under 18 years of age who are infected by the SARS-CoV-2 virus (confirmed diagnosis through reverse transcriptase-polymerase chain reaction [RT-PCR]) while under treatment at pediatric oncology centers. The variables of interest included clinical symptoms, diagnostic and therapeutic measures. The repercussions of SARS-CoV-2 infection on cancer treatment and general prognosis were monitored. RESULTS: One hundred seventy-nine patients were included (median age 6 [4-13] years, 58% male). Of these, 55.9% had acute leukemia and 34.1% had solid tumors. The presence of SARS-CoV-2 was diagnosed by RT-PCR. Various laboratory markers were analyzed, but showed no correlation with outcome. Children with low or high BMI for age had lower overall survival (71.4% and 82.6%, respectively) than those with age-appropriate BMI (92.7%) (p = .007). The severity of presentation at diagnosis was significantly associated with outcome (p < .001). Overall mortality in the presence of infection was 12.3% (n = 22). CONCLUSION: In children with cancer and COVID-19, lower BMI was associated with worse prognosis. The mortality in this group of patients (12.3%) was significantly higher than that described in the pediatric population overall (∼1%).

Surgical Management of Symptomatic Lumbar, Sacral, and Lumbosacral Plexus Tumors: a Peripheral Nerve Unit Experience.

OBJECTIVE: Data concerning the surgical treatment of lumbosacral plexus tumors (LSPTs) is scarce. This study aims to present our experience with a series of 19 patients surgically treated for symptomatic LSPTs at our institution. METHODS: This is a retrospective study of 19 patients surgically treated for symptomatic LSPTs from 2011 to 2019. Clinical data were retrieved from medical records and consisted of age, gender, clinical presentation, location of the lesion, surgical approach, final histopathologic diagnosis, follow-up time, outcomes, and complications. RESULTS: Nineteen surgical procedures were conducted. Thirteen patients were female and six, male. The median age of patients was 45 years (range 20 to 63 years). No patients harbored genetic syndromes. Surgical treatment appears to be correlated to the reduction of pain in patients with peripheral nerve sheath tumors (PNSTs), as assessed by visual analog scale (VAS). Sixteen patients did not present with new-onset deficits during follow-up (84.2%), two of whom recovered from their preoperative deficit. Four patients presented with postoperative weakness. The histopathological diagnoses were 11 schwannomas, four neurofibromas, three metastases, and one lymphoma. CONCLUSIONS: LSPTs are rare. When surgical treatment is indicated, it usually requires multidisciplinary management. Surgery appears to be effective concerning the reduction of pain in PNSTs and may also recover neurological deficits. Iatrogenic neurological deficits are an evident risk, such that intraoperative multimodal monitoring should always be performed if available. In lesions involving the sacral plexus, we found it to be indispensable.

[Self-perceived health in Spanish and Portuguese young seniors after the great recession according to the European Health Survey: A cross-sectional study]. / Salud autopercibida en ancianos jóvenes españoles y portugueses tras la recesión según la Encuesta Europea de Salud: un estudio transversal.

OBJECTIVE: The aim of this study is to describe self-perceived health (SPH) in Spanish and Portuguese population aged between 65 and 74years old and to analyze other associated factors measured in the European Health Interview Survey (EHIS) in 2014. DESIGN: Retrospective secondary data analysis from EHIS 2014. SETTING: Community based. PARTICIPANTS: Young seniors, people aged 65-74years old surveyed and with available data from two countries. MAIN MEASUREMENTS: For each country and sex, SPH, sociodemographic variables, clinical chronic conditions, lifestyles and utilization of health care resources were described. A multiple logistic regression (very good or good SPH versus remaining levels) with robust estimators was used to assess the country effect adjusted by sociodemographic factors, clinical factors and/or lifestyles. RESULTS: Good SPH showed variation by country (52.9% Spain vs. 19% Portugal; P<.001) and gender (44% men vs. 31.3% women; P<.001). Both countries had high prevalence of multimorbidity (64.7% Spain vs. 76.3% Portugal; P<.001) and the distribution of chronic diseases was similar with the only exception of depression (13.2% Spain vs. 20.3% Portugal; P<.001). Regarding individual factors related with good SPH we found Spanish nationality (OR: 4.52; 95%CI: 4.05-5.04), male gender (OR: 1.10; 95%CI: 1.101-2.21), education level, completing primary school (OR: 1.28; 95%CI: 1.24-1.31) or achieving tertiary level (OR: 2.43; 95%CI: 1.14-5.17) and physical activity of two or more days per week (OR: 1.87; 95%CI: 1.39-2.5). Factors with a negative impact on SPH were multimorbidity (OR: 0.19; 95%CI: 0.12-0.31) and depression (OR: 0.32; 95%CI: 0.25-0.41). DISCUSSION: Good SPH is higher in Spanish young seniors compared to Portuguese. Having higher level of education achieved and practicing regular physical exercise were two most important factors increasing good SPH.

Impact of contact lens materials on the mfERG response of the human retina.

PURPOSE: To investigate the effect of different hydrophilic and rigid gas-permeable contact lens (CL) materials on multifocal electroretinography (mfERG). METHODS: The mfERG was recorded in 18 healthy subjects with RETI-port/scan21™: 11 subjects underwent mfERG recording wearing two different hydrophilic CLs with different water contents in a randomized order (1 silicone hydrogel-Comfilcon A, 48%EWC, and 1 hydrogel-Omafilcon A, 62% EWC) and 7 other subjects wore a hydrophobic rigid gas-permeable scleral lens (SL)-Hexafocon A. Control measures were recorded without CL in both groups. mfERG recordings were performed with a stimulus array pattern of 103-scaled hexagons displayed on a 19-inch RGB monitor at 28 cm distance at a frame rate of 60 Hz. The amplitude (nV), implicit time and response density (nV/deg2) of the first-order kernel components N1, P1 and N2 were evaluated for the total mfERG response and for the response averages of 4 quadrants and of 6 successive concentric rings. Subjects were optically corrected for the working distance of ERG display. RESULTS: Hydrophobic material significantly decreased the P1 amplitude of the total mfERG response, at Rings 3, 4 and 6 and Quadrant 4 (> 53.77 ± 43.2 nV; P ≤ 0.050), as well as the total (- 71.59 ± 50.68 nV) and Ring 6 (- 104.76 ± 79.88 nV) N2 amplitude (P ≤ 0.043). N1, P1 and N2 peak times suffered significant changes with both hydrophilic CL (P ≤ 0.050). Omafilcon A significantly increased P1 amplitude of Ring 5 and N2 amplitude of Ring 4, when compared to baseline (52.40 ± 71.87 nV; P = 0.036) and to Comfilcon A (39.51 ± 48.63 nV; P = 0.023), respectively. CONCLUSIONS: Hydrophobic CL slightly attenuated the strength of the mfERG signal, especially at the middle to peripheral retinal areas, while hydrophilic CL slightly changed the implicit time of the response. Different hydrophilic CL materials might affect the mfERG response differently. When considering the measurement of mfERG obtained with a CL in place, researchers should bear in mind that some changes can be related to CL material.

Cognitive Impairment in Patients with Ankylosing Spondylitis.

BACKGROUND: Little is known about the potential systemic effects of ankylosing spondylitis (AS) on the nervous system. We designed a study aiming to assess the frequency and clinical predictors of cognitive impairment in AS patients. METHODS: We carried out a cross-sectional case-control study composed of consecutive patients with AS. Trained and blinded interviewers registered clinical-epidemiological data and applied a standardized neurological assessment for each subject of the study. At baseline, functional limitations were characterized using the Health Assessment Questionnaire. Cognitive impairment was evaluated with the Brief Cognitive Screening Battery, the Montreal Cognitive Assessment, and the Clinical Dementia Rating, while neuropsychiatric symptoms were investigated with the Hospital Anxiety and Depression Scale. Healthy controls were matched for age, educational attainment, sex, and comorbidities. We compared the neurological outcomes between case and controls, and we determined the clinical predictors of cognitive decline. RESULTS: We included 40 patients (mean: 49.3 years) with AS and 40 healthy controls (mean: 48.8 years) in our study. In Brief Cognitive Screening Battery, patients with AS presented a statistically significant poor performance in the clock drawing test and in the verbal fluency. The mean Montreal Cognitive Assessment (MoCA) scores were significantly lower in AS subjects compared to the control group. Also, the prevalence of subjects classified as cognitively impaired according to MoCA was significantly higher in the AS group (90.0% vs. 57.5%, p = 0.02). Moreover, neuropsychiatric symptoms were more prevalent in AS patients. Worse functional limitations were associated with poor cognitive performance as well. CONCLUSIONS: Patients with AS might be more vulnerable to cognitive decline.

Clinical Findings and Ocular Symptoms Over 1 Year in a Sample of Scleral Lens Wearers.

PURPOSE: To report the fitting aspects, clinical findings, and symptoms over 12 months of scleral lens (SL) wear. METHODS: Sixty-nine patients with irregular cornea due to ectasia or surgical procedures (IC group) or regular corneas with high ametropia (RC group) completed the 12-month prospective follow-up period. Patients were evaluated at baseline, lens dispensing visit, 1 month, 3 months, 6 months, and 12 months for assessment of comfort, fitting aspects, and slitlamp findings. Comfort was assessed with the Ocular Surface Disease Index (OSDI) questionnaire and Dry Eye Questionnaire. Slitlamp evaluations comprised on-eye lens fitting (lens alignment and tear reservoir thickness) and anterior ocular surface health after removing the lens (edema, hyperemia, staining, and adverse events). RESULTS: OSDI Scores were significantly reduced after 1 month of SL wear comparing to baseline (from 47.0±22.7-23.9±14.7 in IC group, P<0.001 and 27.0±16.1-17.0±13.7, P=0.029 in RC group, P<0.05), without statistical significant differences from 1 to 12 months. Tear reservoir thickness showed a significant reduction at V1m (122 µm on IC group and 126 µm in RC group, P<0.05), that continued over time until V12m (195 and 184 µm lower compared with Baseline (P<0.05, Wilcoxon). Hyperemia and staining were significantly higher after SL removal when compared with baseline (P<0.05), and maintained the same behavior over the 12 months. There were no severe adverse events during the entire follow-up period. CONCLUSIONS: Comfort enhancement promoted by SL remained over the entire follow-up. Despite no severe adverse events recorded over the 12 months of follow-up, higher hyperemia and staining grades were found after SL removal when compared with no-lens condition.

Lapatinib, Nilotinib and Lomitapide Inhibit Haemozoin Formation in Malaria Parasites.

With the continued loss of antimalarials to resistance, drug repositioning may have a role in maximising efficiency and accelerating the discovery of new antimalarial drugs. Bayesian statistics was previously used as a tool to virtually screen USFDA approved drugs for predicted ß-haematin (synthetic haemozoin) inhibition and in vitro antimalarial activity. Here, we report the experimental evaluation of nine of the highest ranked drugs, confirming the accuracy of the model by showing an overall 93% hit rate. Lapatinib, nilotinib, and lomitapide showed the best activity for inhibition of ß-haematin formation and parasite growth and were found to inhibit haemozoin formation in the parasite, providing mechanistic insights into their mode of antimalarial action. We then screened the USFDA approved drugs for binding to the ß-haematin crystal, applying a docking method in order to evaluate its performance. The docking method correctly identified imatinib, lapatinib, nilotinib, and lomitapide. Experimental evaluation of 22 of the highest ranked purchasable drugs showed a 24% hit rate. Lapatinib and nilotinib were chosen as templates for shape and electrostatic similarity screening for lead hopping using the in-stock ChemDiv compound catalogue. The actives were novel structures worthy of future investigation. This study presents a comparison of different in silico methods to identify new haemozoin-inhibiting chemotherapeutic alternatives for malaria that proved to be useful in different ways when taking into consideration their strengths and limitations.

Age-Related Variations in Corneal Asphericity and Long-Term Changes.

PURPOSE: Corneal front-surface asphericity is directly related with the optical quality of the eye and with contact lenses fitting. The purpose of this study was to evaluate the corneal asphericity as a function of age, sex, and refractive error measured with autokeratometry and corneal topography and its long-term changes (5- to 10-year period). METHODS: The asphericity and corneal curvature were obtained with the autorefractometer/autokeratometer NIDEK ARK-700A and with the videokeratoscope MODI 2.0 and compared. Corneal asphericity was retrospectively analyzed with NIDEK ARK-700A. The longitudinal study of asphericity was conducted with the same device between 2 appointments within an interval of 5 to 10 years. RESULTS: NIDEK ARK-700A showed agreement of asphericity values with those of MODI 2.0 (P=0.172) for a 7-mm diameter chord. The mean Q value of 1,484 right eyes (58.6% female), with a mean age of 40.2±18.4 years, was -0.24±0.12. No differences were found for Q value between sexes (P=0.424), age groups (P=0.268), and refractive error groups (P=0.107). The longitudinal analysis of corneal asphericity in 190 eyes (62.1% female) over a mean period of 5.9±1.4 years showed no significant differences in the Q value (0.00±0.08, P=0.813) over time. However, 14% showed asphericity changes of ±0.10 or higher while 86% of the subjects showed a change below ±0.10. CONCLUSIONS: The mean Q value observed in this study agrees with the average values of a white population and contributes to slightly reduce the positive spherical aberration of the eye. For the large majority of this population, the asphericity did not show significant changes within a period of 5 to 10 years, but significant changes can be observed in some patients.