Imbalanced IL10/TGF-ß production by regulatory T-lymphocytes in patients with HTLV-1-associated myelopathy/ tropical spastic paraparesis.

BACKGROUND: Human T-cell lymphotropic virus type 1 (HTLV-1), also denominated Human T-cell leukemia virus-1, induces immune activation and secretion of proinflammatory cytokines, especially in individuals with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Regulatory T lymphocytes (Tregs) may control of inflammation through the production of regulatory cytokines, including IL10 and TGF-ß. In this study we determined the frequencies of CD4 + and CD8 + Tregs in a HAM/TSP population, compared to asymptomatic carriers and uninfected individuals, as well as investigated the profiles of regulatory and inflammatory cytokines. METHODS: Asymptomatic HTLV-1 carriers and HAM/TSP patients were matched by sex and age. The frequencies of IL10- and/or TGF-ß-producing Tregs were quantified by flow cytometry. Real-time reverse transcription polymerase chain reaction (RT-PCR) was used to quantify HTLV-1 proviral load and the mRNA expression of cytokines and cellular receptors in peripheral blood mononuclear cells. RESULTS: Total frequencies of CD4 + Tregs, as well as the IL10-producing CD4 + and CD8 + Treg subsets, were statistically higher in patients with HAM/TSP compared to asymptomatic HTLV-1-infected individuals. In addition, a positive correlation was found between the frequency of CD4 + IL10 + Tregs and proviral load in the HAM/TSP patients evaluated. A positive correlation was also observed between gene expression of proinflammatory versus regulatory cytokines only in HAM / TSP group. CONCLUSIONS: A higher frequencies of IL10-producing Tregs were identified in patients with HAM/TSP. Imbalanced production of IL10 in relation to TGF-ß may contribute to the increased inflammatory response characteristically seen in HAM/TSP patients.

LONG-TERM VISUAL OUTCOMES AND OPTICAL COHERENCE TOMOGRAPHY BIOMARKERS IN EYES WITH MACULAR EDEMA SECONDARY TO RETINAL VEIN OCCLUSION FOLLOWING ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY.

PURPOSE: To evaluate the structural characteristics and long-term visual outcomes in eyes impacted by macular edema as a consequence of retinal vein occlusion that has undergone effective treatment with anti-vascular endothelial growth factor therapy. METHODS: Inclusion criteria comprised 42 eyes of 41 patients, subjected to long-term follow-up, displaying resolved macular edema after a minimum of 5 years since the commencement of anti-vascular endothelial growth factor therapy. During the final visit, two experienced observers evaluated several qualitative parameters using spectral-domain optical coherence tomography, such as the integrity of the external limiting membrane, the state of the ellipsoid zone and retinal pigment epithelium, and the presence of disorganization of the retinal inner layers. In addition, a quantitative evaluation of the inner and outer retinal thicknesses was conducted for the purpose of topographical analysis. RESULTS: The most prominent qualitative correlation identified with best-corrected visual acuity during the final visit was connected to the presence of disorganization of the retinal inner layers ( P = 0.004) and the integrity of the external limiting membrane ( P = 0.015). In relation to quantitative aspects, a noteworthy correlation was noted between the visual acuity during the last visit and the parafoveal thickness in both the inner ( P = 0.003) and outer retina ( P = 0.018). CONCLUSION: In eyes where macular edema resulting from retinal vein occlusion has been successfully resolved with anti-vascular endothelial growth factor therapy, changes in the status of the external limiting membrane and the presence of disorganization of the retinal inner layers serve as valuable optical coherence tomography biomarkers, indicating prolonged visual outcomes.

Prevalence and characteristics of HTLV-associated uveitis in patients from Bahia, an endemic area for HTLV - 1 in Brazil.

BACKGROUND: HTLV-1-associated uveitis (HAU) is an inflammatory reaction of the choroid, retina, optic nerve and vitreous that can lead to vision impairment. The worldwide prevalence of HAU varies widely. OBJECTIVE: To determine the prevalence of HAU in patients from Salvador, Bahia-Brazil, and describe uveitis type and associated symptoms. METHODS: Cross-sectional analytical study to determine the prevalence of uveitis in HTLV-1-infected patients recruited in Bahia, Brazil, a region considered endemic for HTLV-1. Patients were enrolled at a local reference center for HTLV (infected) and at an outpatient ophthalmology clinic (noninfected group). All patients were examined by the same ophthalmologist following a single protocol. Prevalence ratios (PR) were calculated. RESULTS: A total of 168 consecutively examined HTLV-1-infected patients and 410 noninfected patients (randomly selected) were included. Females predominated (82.1%) in the HTLV-1-infected group (versus 64.4% in the uninfected group) (p < 0.001). The mean age of infected and uninfected patients was 53.2 and 62.8 years, respectively (p < 0.001). The prevalence of uveitis in HTLV-1+ and HTLV-1- patients was 7.14% and 0.73%, respectively (PR = 9.76; 95CI%:2.79-34.15; p < 0.01). Bilateral intermediate uveitis, associated with symptoms including visual disturbances and floaters, was most commonly identified in the HTLV-1-infected patients, whereas unilateral anterior uveitis, in association with symptoms such as blurring and ocular pain, was more common in the uninfected group. CONCLUSION: The prevalence of uveitis in patients with HTLV-1 was markedly higher than in uninfected subjects. HAU patients were mostly asymptomatic and exhibited bilateral presentation, with uveitis more frequently localized in the intermediate chamber.

NK Cell Responses in Zika Virus Infection Are Biased towards Cytokine-Mediated Effector Functions.

Zika virus (ZIKV) is a mosquito-borne flavivirus that has emerged as a global concern because of its impact on human health. ZIKV infection during pregnancy can cause microcephaly and other severe brain defects in the developing fetus and there have been reports of the occurrence of Guillain-Barré syndrome in areas affected by ZIKV. NK cells are activated during acute viral infections and their activity contributes to a first line of defense because of their ability to rapidly recognize and kill virus-infected cells. To provide insight into NK cell function during ZIKV infection, we have profiled, using mass cytometry, the NK cell receptor-ligand repertoire in a cohort of acute ZIKV-infected female patients. Freshly isolated NK cells from these patients contained distinct, activated, and terminally differentiated, subsets expressing higher levels of CD57, NKG2C, and KIR3DL1 as compared with those from healthy donors. Moreover, KIR3DL1+ NK cells from these patients produced high levels of IFN-γ and TNF-α, in the absence of direct cytotoxicity, in response to in vitro stimulation with autologous, ZIKV-infected, monocyte-derived dendritic cells. In ZIKV-infected patients, overproduction of IFN-γ correlated with STAT-5 activation (r = 0.6643; p = 0.0085) and was mediated following the recognition of MHC class 1-related chain A and chain B molecules expressed by ZIKV-infected monocyte-derived dendritic cells, in synergy with IL-12 production by the latter cells. Together, these findings suggest that NK cells contribute to the generation of an efficacious adaptive anti-ZIKV immune response that could potentially affect the outcome of the disease and/or the development of persistent symptoms.

Low dialysate sodium in children and young adults on maintenance hemodialysis: a prospective, randomized, crossover study.

BACKGROUND: The optimal dialysate sodium concentration (dNa) in children on hemodialysis (HD) is unknown. The aim of this study was to compare the effect on interdialytic weight gain (IDWG) and blood pressure (BP) of a low (135 mmol/l) and standard dNa (138 mmol/l) in children and young adults on maintenance HD. METHODS: This prospective single-blind randomized crossover study consisted of a randomized sequence of two phases: "standard dNa" of 138 mmol/L and "low dNa" of 135 mmol/L. Each phase lasted 4 weeks. Inclusion criteria were age < 25 years, hypertension, pre-HD serum Na (sNa) ≥ 130 mmol/L, and occurrence of symptoms in less than 25% of sessions. Primary outcomes were pre-HD systolic and diastolic BP and IDWG. RESULTS: Fifteen patients were recruited, mean age 17.8 ± 4.4 years. Pre-HD SBP and DBP were not different between the two treatments. Mean IDWG was significantly lower with low dNa than with standard dNa: 2.12 ± 1.39% vs. 2.77 ± 1.53%, respectively (p = 0.008). The first-hour refill index (a volume index based on blood-volume monitoring) was significantly lower with dNa 135 mmol/L (p = 0.018). The mean Na gradient (dNa-sNa) was - 2.53 ± 2.4 mmol/L with dNa 135 mmol/L and 0.17 ± 2.8 mmol/L with dNa 138 mmol/L (p = 0.0001). The incidence of symptomatic sessions was similar (1.0% vs. 1.0%). CONCLUSIONS: In a selected population of hypertensive pediatric and young adult HD patients, a dNa of 135 mmol/L was associated with a significant reduction of IDWG compared with a dNa of 138 mmol/L. Furthermore, long-term studies are needed to investigate the effect of lowering dNa on BP. A higher resolution version of the Graphical abstract is available as Supplementary information.

Sodium intake and urinary losses in children on dialysis: a European multicenter prospective study.

BACKGROUND: Sodium (Na) balance is unexplored in dialyzed children. We assessed a simplified sodium balance (sNaB) and its correlates in pediatric patients receiving maintenance dialysis. METHODS: Patients < 18 years old on hemodialysis (HD) or peritoneal dialysis (PD) in six European Pediatric Dialysis Working Group centers were recruited. sNaB was calculated from enteral Na, obtained by a 3-day diet diary, Na intake from medications, and 24-h urinary Na (uNa). Primary outcomes were systolic blood pressure and diastolic blood pressure standard deviation scores (SBP and DBP SDS), obtained by 24-h ambulatory blood pressure monitoring or office BP according to age, and interdialytic weight gain (IDWG). RESULTS: Forty-one patients (31 HD), with a median age of 13.3 (IQR 5.2) years, were enrolled. Twelve patients (29.3%) received Na-containing drugs, accounting for 0.6 (0.7) mEq/kg/day. Median total Na intake was 1.5 (1.1) mEq/kg/day, corresponding to 60.6% of the maximum recommended daily intake for healthy children. Median uNa and sNaB were 0.6 (1.8) mEq/kg/day and 0.9 (1.7) mEq/kg/day, respectively. The strongest independent predictor of sNaB in the cohort was urine output. In patients receiving HD, sNaB correlated with IDWG, pre-HD DBP, and first-hour refill index, a volume index based on blood volume monitoring. sNaB was the strongest predictor of IDWG in multiple regression analysis (ß = 0.63; p = 0.005). Neither SBP SDS nor DBP SDS correlated with sNaB. CONCLUSIONS: Na intake is higher than uNa in children on dialysis, and medications may be an important source of Na. sNaB is best predicted by urine output in the population, and it is a significant independent predictor of IDWG in children on HD. A higher resolution version of the Graphical abstract is available as Supplementary information.

SEVERE VISUAL LOSS DURING ANTI-VEGF INTRAVITREAL INJECTIONS IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: TIMING, PROGNOSIS, AND OPTICAL COHERENCE TOMOGRAPHY FINDINGS.

PURPOSE: Intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) is the standard of care for neovascular age-related macular degeneration (nAMD). However, a small subgroup of patients still experience severe visual impairment, which may be related to the number of IVI administered. METHODS: This retrospective observational study analyzed data from patients with sudden severe visual decline (≥15 Early Treatment Diabetic Retinopathy Study [ETDRS] letters loss between two consecutive IVIs) during anti-VEGF treatment for nAMD. Best-corrected visual acuity examination, optical coherence tomography (OCT), and OCT angiography (OCTA) were performed before every IVI and central macular thickness (CMT) and drug injected were collected. RESULTS: 1,019 eyes received anti-VEGF IVI for nAMD from December 2017 to March 2021. Severe VA loss occurred in 15.1% after a median of 6 (range 1-38) IVI. Ranibizumab was injected in 52.8% and aflibercept in 31.9% of cases. Functional recovery after 3 months was significant, without further improvement at 6 months. Visual prognosis relative to the percentage of CMT change showed better visual outcome in eyes with no substantial change in CMT compared with an increase of >20% or a decrease of >5%. CONCLUSION: In this first real-life study exploring severe VA loss during anti-VEGF treatment in patients with nAMD, it was found that it was not unusual for a ≥15 ETDRS letters loss to occur between two consecutive IVIs, often within 9 months of diagnosis and 2 months after the last IVI. Close follow-up and a proactive regimen should be preferred, at least in the first year.

Prosopamnesia: a case report of amnesia for faces.

Prosopamnesia is a face-selective memory disorder in which face learning is impaired, while face-perception disorder (prosopagnosia) and memory disorders for stimuli other than faces are not present. To date, only two cases of prosopamnesia have been reported in adults - one congenital and one secondary to brain damage. This article reports a case of a 68-year-old woman complaining difficulties recognizing persons she had got to know recently. Neuropsychological examination revealed face-specific anterograde amnesia in the absence of prosopagnosia and other memory impairments. Brain MRI did not present any focal abnormality; PET-scan revealed hypoactivation mostly in the frontotemporal area bilaterally. This patient represents the first case of late-onset primary prosopamnesia.

Mid-term safety and effectiveness of intravitreal dexamethasone implant to treat persistent cystoid macular edema in vitrectomized eyes for bacterial endophthalmitis.

PURPOSE: To evaluate the mid-term safety and effectiveness of intravitreal dexamethasone implant (DEX-i) for treating unresponsive to medical therapy cystoid macular edema (CME) in vitrectomized eyes for endophthalmitis. METHODS: Retrospective and interventional case series study conducted on vitrectomized eyes for endophthalmitis that developed a CME that did not adequately respond to medical therapy, who underwent 0.7-mg DEX-i. Main outcome measures were changes in central retinal thickness (CRT) and best corrected visual acuity (BCVA). RESULTS: Eleven eyes were included in the study. Microbiological findings of vitreous biopsies were 7 (63.6%) staphylococcus epidermidis; 3 (27.3%) Pseudomonas aeruginosa; and 1 (9.1%) Propionibacterium acnes. Median (interquartile range, IqR) duration of CME was 4.0 (3.0-4.0) months. Median (IqR) time between vitrectomy and DEX-i was 9.0 (9.0-11.0) months. Median CRT was significantly decreased from 548.0 (412.8-572.5) µm at baseline to 308.0 (281.3-365.5) µm at month 6 (p = 0.0009, Friedman test). Median BCVA significantly improved from 38.0 (30.5-44.8) letters at baseline to 50.0 (46.8-53.0) letters at month 6 (p < 0.0001, Friedman), with 9 (81.8%) eyes gaining ≥ 10 letters. Elevation of intraocular pressure was observed in one (9.1%) eye, which was successfully controlled with medical therapy. No recurrence of endophthalmitis or other complications was observed. Eight (72.7%) eyes required an additional DEX-i, while 3 (27.3%) were successfully controlled with only one DEX-i. CME recurrence occurred in 5 (62.5%) Gram-positive and 3 (100.0%) Gram-negative bacteria (p = 0.2357). CONCLUSION: In vitrectomized eyes for endophthalmitis affected by CME unresponsive to medical therapy, DEX-i had an acceptable safety profile and achieved favorable outcomes. The possibility of suppressing mechanisms for infection control should be taken into account, although correct management of endophthalmitis and long time without reactivation before DEX-i reduce the risk.

The role of experience in parenting beliefs of British and Italian women during pregnancy.

To understand the role of experience in parenting beliefs about caring for infants, we examined the parenting beliefs of pregnant women who were expecting their first child with those of pregnant women who already had at least one other child. A culturally diverse sample of 550 British and Italian women completed self-report measures evaluating their beliefs about the value of attunement and structure in caregiving, parenting self-efficacy, and home chaos. Psychometric evaluation confirmed the two-factor structure of the Baby Care Questionnaire (BCQ) for measuring attunement and structure but did not support configural invariance across the different samples. Beliefs about attunement and structure were related to parenting experience: pregnant women who already had at least one other child reported stronger beliefs in attunement, whereas pregnant women expecting their first child reported stronger beliefs in structure. Regression analyses revealed that the associations between parenting beliefs and experience remained when controlling for country, age, and education. Despite the limitations imposed by the lack of configural invariance, this cross-sectional, cross-cultural study constitutes an important first step in examining the relations between parenting experience and parenting beliefs during pregnancy.

Para comprender el papel de la experiencia en las creencias de crianza sobre el cuidado de los infantes, examinamos las creencias de crianza de mujeres embarazadas que esperaban su primer niño con aquellas de mujeres embarazadas que ya tenían por lo menos otro niño. Un grupo muestra culturalmente diverso de quinientas cincuenta mujeres británicas e italianas completó medidas auto reportadas de evaluación de sus creencias acerca del valor de la coordinación armónica y la estructura en cuanto al cuidado, la auto efectividad de la crianza, así como el caos en casa. La evaluación sicométrica confirmó la estructura de dos factores del Cuestionario de Cuidado del Bebé (BCQ: Winstanley y Gattis, 2013) para medir la coordinación armónica y la estructura, pero no apoyó la invariabilidad configuracional a través de los diferentes grupos muestra. Las creencias acerca de la coordinación armónica y la estructura se relacionaron con la experiencia de la crianza: las mujeres embarazadas que ya tenían por lo menos otro niño reportaron creencias más fuertes en cuanto a la coordinación armónica, mientras que las mujeres embarazadas que esperaban su primer niño reportaron creencias más fuertes en cuanto a la estructura. Los análisis de regresión revelaron que las asociaciones entre las creencias de crianza y la experiencia se mantenían siendo las mismas cuando se usaron los controles referentes a país, edad y educación. A pesar de las limitaciones impuestas por la falta de la invariabilidad configuracional, este estudio interseccional constituye un importante paso en el examen de las relaciones entre la experiencia de crianza y las creencias sobre la crianza durante el embarazo.

Afin de comprendre le rôle de l'expérience dans les croyances de parentalité sur la manière de prendre soin des bébés, nous avons examiné les croyances de parentalité de femmes enceintes qui attendaient leur premier enfant avec celles de femmes enceintes ayant déjà eu au moins un enfant. Un échantillon culturellement divers de cinq cent cinquante femmes britanniques et italiennes ont rempli des mesures auto-rapportées évaluant leurs croyances concernant la valeur de l'harmonisation et de la structure dans les soins à l'enfant, l'auto-efficacité de parentalité, et le chaos à domicile. L'évaluation psychométrique a confirmé la structure à deux facteurs du Questionnaire du Soin au Bébé (abrégé BCQ en anglais; Winstanley & Gattis, 2013) pour la mesure de l'harmonisation et de la structure mais n'a pas soutenu l'invariance de configuration au travers des différents échantillons. Les croyances sur l'harmonisation et la structure étaient liées à l'expérience de parentalité: les femmes enceintes qui avaient déjà eu un enfant ont fait état de croyances plus fortes dans l'harmonisation, alors que les femmes enceintes attendant leur premier enfant ont fait état de croyances plus fortes dans la structure. Des analyses de régression ont révélé que les liens entre les croyances de parentalité et l'expérience demeuraient quand on contrôlait pour le pays, l'âge et l'éducation. En dépit des limitations imposées par le manque d'invariance de configuration, cette étude transversale et multiculturelle constitue une étape importante dans l'examen des relations entre l'expérience de parentalité et les croyances de parentalité durant la grossesse.

Association between high proviral load, cognitive impairment, and white matter brain lesions in HTLV-1-infected individuals.

The association between high proviral load (PVL) in peripheral blood mononuclear cells (PBMC), cognitive disturbance and white matter brain lesions in HTLV-1-infected individuals is still undefined. A cross-sectional study included 62 participants: 22 asymptomatic carriers (mean age 43.4 ± 13.1 years old), 22 patients with HTLV-1-associated myelopathy (HAM/TSP) (mean age 51.5 ± 8.7 years old), and 18 uninfected controls (mean age 52.3 ± 11.1 years old). All individuals fulfilled the following criteria: between 18 and 65 years of age, more than 4 years of formal education, and completed neuropsychological evaluation and HTLV-1 serology. Infected individuals underwent brain conventional magnetic resonance imaging and PVL quantitative PCR (qPCR). Statistical analysis was adjusted in the models by age and education. Cognitive deficit was observed in all groups. Patients with HAM/TSP showed higher neurocognitive deviation in attention and motor skills, higher frequency (84%) of brain white matter lesions, and higher PVL median (range) 8.45 (0.5-71.4) copies/100 PBMC. Brain white matter lesion was associated with verbal memory deficit in HTLV-1-infected individuals (HAM/TSP and asymptomatic carriers) (p = 0.026). In addition, there was a correlation between higher PVL and neurocognitive dysfunction score (processing speed of visuomotor information and visuoconstructive praxis) in HTLV-1-infected patients. The study demonstrates an association between HTLV-1 infection, neurocognitive disorder, and white matter brain lesions on MRI as well as a correlation with higher HTLV-1 PVL, suggesting that the central nervous system involvement by HTLV-1 is not restricted to the spinal cord but involves the whole neuro-axis. HTLV-1-infected individuals should be tested for cognitive impairment.

Nutritional status and volume control in adolescents on chronic hemodialysis.

BACKGROUND: Pediatric patients on maintenance hemodialysis (HD) are at risk of both malnutrition and fluid overload. This pilot study aimed to assess correlates of normalized protein catabolic rate (nPCR) in adolescents on chronic HD, in particular fluid status markers. METHODS: All patients aged 10-18 years on chronic HD in our center between 2017 and 2019 were enrolled. For each patient, mean nPCR was calculated and correlations with the following parameters investigated: dry body weight change in subsequent 3 months in kg (∆BW) and percentage of BW (∆BW%), change in body mass index (∆BMI), preHD systolic and diastolic blood pressure (SBP, DBP), residual urine output, biochemistry, and blood volume monitoring-derived first hour refill index (RI), calculated as ratio between ultrafiltration rate and reduction in relative blood volume in first hour of dialysis. RESULTS: Seventy-nine nPCR determinations were collected in 23 patients, median age 14.8 years. nPCR significantly correlated with ∆BW, ∆BW%, ∆BMI, spKT/V, and preHD serum creatinine, and negatively correlated with age, DBP SDS (r=-0.466, p=0.025) and RI (r=-0.435, p=0.043). RI was significantly higher in patients with nPCR <1 than those with nPCR above this threshold: 3.2 (1.9-4.7) vs. 1.4 (0.7-1.8) ml/kg/h/% (p=0.021). At multivariable analysis, nPCR remained positively correlated with creatinine and spKt/V, and inversely correlated with RI. CONCLUSIONS: nPCR is a significant predictor of weight change in adolescents on maintenance HD, and seems associated with creatinine and dialysis adequacy. Inverse correlation with RI suggests possible associations between malnutrition and fluid overload, but larger prospective studies are needed to confirm this. A higher resolution version of the Graphical abstract is available as Supplementary information.

DIABETIC MACULAR EDEMA AND CATARACT SURGERY: Phacoemulsification Combined With Dexamethasone Intravitreal Implant Compared With Standard Phacoemulsification.

PURPOSE: To compare functional and anatomical results of combined phacoemulsification and dexamethasone intravitreal implant (Ozurdex; DEX-I) with standard phacoemulsification in diabetic patients with cataract. METHODS: Retrospective, comparative, cohort study. Patients with nonproliferative diabetic retinopathy, macular edema, and cataract, treated routinely at the Eye Clinic, Azienda Ospedaliero Universitaria Policlinico, Bari, Italy with phacoemulsification associated with DEX-I (n = 23; Phaco-Dex) or standard phacoemulsification (n = 23; Phaco-alone). Best-correct visual acuity, central subfield thickness, and intraocular pressure were assessed at baseline and monthly for 3 months after surgery, and t-test was used to assess change from baseline. A multilevel regression model with an unstructured correlation-type matrix to account for repeated data measures was used for statistical analysis in and between groups. RESULTS: With Phaco-Dex, best-correct visual acuity increased significantly from the first month (P = 0.0005 vs. baseline) and remained stable at the following visits; central subfield thickness decreased significantly from Month 2 (P = 0.049 and P = 0.04 vs. baseline, respectively); at each timepoint, central subfield thickness was significantly lower in the Phaco-Dex group versus Phaco-alone. Intraocular pressure increased significantly during follow-up (P = 0.001 at Month 3 vs. baseline) but remained within the normal range. In the Phaco-alone group, best-correct visual acuity, and intraocular pressure did not show any significant changes after surgery, whereas central subfield thickness increased from Month 2 (P = 0.05 vs. baseline). CONCLUSION: In diabetic patients with macular edema and visually significant cataract, combined treatment with phacoemulsification and DEX-I seemed to be effective, safe, and superior to standard phacoemulsification considering both functional and tomographic parameters.

HIV/Aids and COVID-19 in Brazil: in four decades, two antithetical approaches to face serious pandemics.

In the space of four decades, Brazil has faced two serious pandemics: human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and Coronavirus disease 2019 (COVID-19). The country's response to HIV/AIDS was coordinated by several stakeholders and recognised the importance of scientific evidence in guiding decision-making, and a network offering monitoring and antiretroviral treatment was provided through coordinated efforts by the country's universal health system. Conversely, the lack of a centrally coordinated strategy and misalignment between government ministries regarding the COVID-19 pandemic response, together with the denial of scientific evidence, promotion of ineffective treatments and insufficient vaccination efforts, have all led to the uncontrolled spread of infection, the near-total collapse of the health system and excess deaths.

Genetic Polymorphisms in Patients With Systemic Lupus Erythematosus and Jaccoud Arthropathy: A Pilot Study.

INTRODUCTION: Jaccoud arthropathy (JA) is a nonerosive and deforming arthropathy experienced frequently by patients with systemic lupus erythematosus (SLE). Although genetic polymorphisms are associated with SLE development, the association between genetic polymorphisms and JA has not been studied to date. The main objective of this study was to evaluate an association between HLA, STAT4, IRF5, and BLK polymorphisms and the presence of JA in Brazilian individuals with SLE. METHODS: Patients were selected from a cohort of individuals with SLE followed at 2 rheumatology reference centers in Salvador, Bahia, Brazil. The JA diagnosis was based on clinical and radiological criteria. The participants were genotyped for rs9271100, rs7574865, rs10488631, and rs13277113 polymorphisms in the HLA, STAT4, IRF5, and BLK genes, respectively, using real-time polymerase chain reaction. The presence of JA was correlated with allele frequencies, and clinical and laboratory data. RESULTS: One hundred forty-four individuals with SLE (38 with JA and 106 with SLE without JA) were studied. The mean age of the patients was 45 ± 12 years; the majority were women and had brown skin. Patients with JA had a longer disease duration than patients without JA. Serositis and neuropsychiatric manifestations were more frequent in the JA population. The A allele of rs13277113 in the BLK gene was associated with the presence of JA. CONCLUSIONS: The rs13277113 polymorphism in the BLK gene was found to be a possible genetic risk for JA development. However, further studies in larger populations should be performed to confirm this finding.

Metabolic Regulation and Development of Energy Cane Setts upon Auxin Stimulus.

Energy cane is a bioenergy crop with an outstanding ability to bud sprouting and increasing yield in ratoon cycles even in marginal lands. Bud fate control is key to biomass production and crop profits due to vegetative propagation and tiller dependency, as well as phenotype plasticity to withstand harsh environmental conditions. During the establishment stage (plant cane cycle), energy cane has a tendency for low root:shoot ratio, which might hamper the ability to cope with stress. Auxin is known to modulate bud sprouting and stimulate rooting in sugarcane. Hence, we treated a slow and a fast bud sprouting energy cane cultivars with auxin or controls (with and without water soaking) for 6 h prior to planting and evaluate plant growth parameters and metabolic profiling using two techniques (gas chromatography with time-of-flight mass spectrometer and nuclear magnetic resonance) to characterize the effect and identify metabolite markers associated with bud inhibition and outgrowth. Auxin inhibited bud burst and promote rooting in setts changing the root:shoot ratio of plantlets. Metabolome allowed the identification of lactate, succinate and aspartate family amino acids as involved in bud fate control through the potential modulation of oxygen and energy status. Investigating environmental and biochemical factors that regulate bud fate can be incremental to other monocot species. Our study provides new insights into bud quiescence and outgrowth in cane hybrids, with the potential to leverage our understanding of yield-related traits, crop establishment and adaptation to global climate change.

General Sleep Disturbance Scale (GSDS-IT) in people with spinal cord injury: a psychometric study.

STUDY DESIGN: Psychometric study. OBJECTIVE: This study sought to analyze the psychometric properties of the Italian version of the General Sleep Disturbance Scale (GSDS-IT) in a population of individuals with spinal cord injury (SCI). SETTING: Italy. METHODS: Its reliability was assessed using the Cronbach's alpha and intraclass correlation coefficient (ICC), while its concurrent validity was assessed using the Pearson's correlation coefficient in relation to the Pittsburgh Sleep Quality Index (PSQI). The obtained scores were compared with the cut-off score for the GSDS-IT among a healthy Italian population (38.5). RESULTS: The GSDS-IT was administered to 57 participants with SCI who were recruited from all over Italy. The GSDS-IT was found to have good internal consistency (Cronbach's α of 0.76) and good test-retest reliability (ICC of 0.7), and it showed positive and significant values for all the PSQI domains. Based on the cut-off score of 38.5, 56% of participants tested positive for sleep disturbances upon admission (t0), while among the randomized participants submitted for the test-retest after 24 h (t1), 75% tested positive for sleep disturbances. CONCLUSION: The GSDS-IT is a valid, reliable, and time-efficient tool for measuring sleep disturbances over the past week in a population with SCI.

Implementation of Lean healthcare methodology in designing an Intravitreal Injection Center: first Italian experience.

PURPOSE: The principles of the Lean methodology, introduced by Toyota to improve productivity, are relevant to other settings, including healthcare. We aimed to use Lean methodology to design a new setting in our ophthalmology clinic to improve the management of patients receiving an intravitreal injection for ocular diseases. METHODS: The location of services, days of operation, scheduling and processing of patients, utilization of staff, data recording methods, and examination and surgical procedures were analyzed, and a new Intravitreal Injection Center was developed according to Lean principles. RESULTS: The new setting, which is confined to a single floor, in contrast to the previous system, which necessitated that patients visit various locations spread over three floors of the hospital, demonstrated benefits for patients and improved the flow and management of patients through the system with a need for fewer team members. The intravitreal injection service improved with regard to both the quality and speed of the overall procedure and the efficient use of staff. CONCLUSION: Our aim to achieve a fast and one-way route to move patients through intravitreal injection administration was achieved, limiting any waste of time and space and improving the capacity management of the center. The system is of relevance to other ophthalmology clinic settings and facilitates the collection of valuable epidemiological and clinical information on the response of patients to different drugs and treatment regimens.

Functional capacity of natural killer cells in HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients.

BACKGROUND: Natural killer (NK) cells are part of the innate immune system and provide surveillance against viruses and cancers. The ability of NK cells to kill virus-infected cells depends on the balance between the effects of inhibitory and activating NK cell receptors. This study aimed to investigate the phenotypic profile and the functional capacity of NK cells in the context of HTLV-1 infection. METHODS: This cross-sectional study sequentially recruited HTLV-1 infected individuals with HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and asymptomatic HTLV-1 (AS) from the Integrated and Multidisciplinary HTLV Center in Salvador, Brazil. Blood samples from healthy blood donors served as controls. NK cell surface receptors (NKG2D, KIR2DL2/KIR2DL3, NKp30, NKG2A, NKp46, TIM-3 and PD-1), intracellular cytolytic (Granzyme B, perforin) and functional markers (CD107a for degranulation, IFN-γ) were assayed by flow cytometry in the presence or absence of standard K562 target cells. In addition, cytotoxicity assays were performed in the presence or absence of anti-NKp30. RESULTS: The frequency of NKp30+ NK cells was significantly decreased in HAM/TSP patients [58%, Interquartile Range (IQR) 30-61] compared to controls (73%, IQR 54-79, p = 0.04). The production of cytolytic (perforin, granzyme B) and functional markers (CD107a and IFN-γ) was higher in unstimulated NK cells from HAM/TSP and AS patients compared to controls. By contrast, stimulation with K562 target cells did not alter the frequency of CD107a+ NK cells in HAM/TSP subjects compared to the other groups. Blockage of the NKp30 receptor was shown to decrease cytotoxic activity (CD107a) and IFN-γ expression only in asymptomatic HTLV-1-infected individuals. CONCLUSIONS: NK cells from individuals with a diagnosis of HAM/TSP present decreased expression of the activating receptor NKp30, in addition to elevated degranulation activity that remained unaffected after blocking the NKp30 receptor.

Performance of Commercially Available Serological Screening Tests for Human T-Cell Lymphotropic Virus Infection in Brazil.

Serological screening for human T-cell lymphotropic virus type 1 (HTLV-1) is usually performed using enzyme-linked immunosorbent assay (ELISA), particle agglutination, or chemiluminescence assay kits. Due to an antigen matrix improvement entailing the use of new HTLV antigens and changes in the format of HTLV screening tests, as well as newly introduced chemiluminescence assays (CLIAs), a systematic evaluation of the accuracy of currently available commercial tests is warranted. We aimed to assess the performance of commercially available screening tests for HTLV infection diagnosis. A diagnostic accuracy study was conducted on a panel of 397 plasma samples: 200 HTLV-negative plasma samples, 170 HTLV-positive plasma samples, and 27 plasma samples indeterminate by Western blotting (WB). WB-indeterminate samples (i.e., those yielding no specific bands for HTLV-1 and/or HTLV-2) were assessed by PCR, and the results were used to compare agreement among the commercially available ELISA screening tests. For performance analysis, WB-indeterminate samples were excluded, resulting in a final study panel of 370 samples. Three ELISA kits (Murex HTLV-1/2 [Murex], anti-HTLV-1/2 SYM Solution [SYM Solution], and Gold ELISA HTLV-1/2 [Gold ELISA]) and one CLIA kit (Architect rHTLV-1/2) were evaluated. All screening tests demonstrated 100% sensitivity. Concerning the HTLV-negative samples, the SYM Solution and Gold ELISA kits had specificity values of >99.5%, while the Architect rHTLV-1/2 test presented 98.1% specificity, followed by Murex, which had a specificity of 92.0%. Regarding the 27 samples with WB-indeterminate results, after PCR confirmation, all ELISA kits showed 100% sensitivity but low specificity. Accuracy findings were corroborated by the use of Cohen's kappa value, which evidenced slight and fair agreement between PCR analysis and ELISAs for HTLV infection diagnosis. Based on the data, we believe that all evaluated tests can be safely used for HTLV infection screening.