Long-term hematopoietic stem cells trigger quiescence in Leishmania parasites.

Addressing the challenges of quiescence and post-treatment relapse is of utmost importance in the microbiology field. This study shows that Leishmania infantum and L. donovani parasites rapidly enter into quiescence after an estimated 2-3 divisions in both human and mouse bone marrow stem cells. Interestingly, this behavior is not observed in macrophages, which are the primary host cells of the Leishmania parasite. Transcriptional comparison of the quiescent and non-quiescent metabolic states confirmed the overall decrease of gene expression as a hallmark of quiescence. Quiescent amastigotes display a reduced size and signs of a rapid evolutionary adaptation response with genetic alterations. Our study provides further evidence that this quiescent state significantly enhances resistance to treatment. Moreover, transitioning through quiescence is highly compatible with sand fly transmission and increases the potential of parasites to infect cells. Collectively, this work identified stem cells in the bone marrow as a niche where Leishmania quiescence occurs, with important implications for antiparasitic treatment and acquisition of virulence traits.

Feline leishmaniasis in an animal shelter in northeastern Brazil: Clinical aspects, coinfections, molecular detection, and serological study of a new recombinant protein.

Infection and clinical cases of leishmaniasis caused by Leishmania infantum in cats have been increasingly reported in several countries, including Brazil. In this study, we used an enzyme-linked immunosorbent assay (ELISA) and an immunochromatographic test (ICT) based on a recombinant antigen (rKDDR-plus) to detect anti-Leishmania antibodies in cats from an animal shelter in northeastern Brazil. We compared the results with an ELISA using L. infantum crude antigen (ELISA-CA). We also investigated the presence of Leishmania DNA in blood or ocular conjunctival samples as well as the association between Leishmania PCR positivity and serological positivity to feline immunodeficiency virus (FIV), feline leukemia virus (FeLV) and Toxoplasma gondii. Concerning serological assays, a higher positivity was detected using the ICT-rKDDR-plus (7.5%; 7/93) as compared to ELISA-rKDDR-plus (5.4%; 5/93) and ELISA-CA (4.3%; 4/93). Upon PCR testing, 52.7% (49/93) of the ocular conjunctival swabs and 48.3% (44/91) of the blood samples were positive. Together, PCR and serological testing revealed overall positivities of 73.1% (68/93) and 12.9% (12/93), respectively. Among PCR-positive samples, 45.5% (31/68) showed co-infection with FIV, 17.6% (12/68) with FeLV, and 82.3% (56/68) with T. gondii. More than half of the PCR-positive cats showed at least one clinical sign suggestive of leishmaniasis (58.8%; 40/68) and dermatological signs were the most frequent ones (45.5%; 31/68). Both tests employing the recombinant antigen rKDDR-plus (i.e., ICT-rKDDR-plus and ELISA-rKDDR-plus) detected more positive cats than the ELISA-CA but presented low overall accuracy. PCR testing using either blood or ocular conjunctival samples detected much more positive cats than serological tests.

HIV pre-exposure prophylaxis and incidence of sexually transmitted infections in Brazil, 2018 to 2022: An ecological study of PrEP administration, syphilis, and socioeconomic indicators.

BACKGROUND: Human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) is one of the pillars of a combination prevention strategy for reducing the risk of new infections caused by HIV. The daily use of antiretroviral drugs by individuals who are not infected with HIV is required to prevent infection. Although its efficacy has been well established in the literature, in recent years, the decreased supply of antiretroviral drugs has been associated with an increase in the incidence of sexually transmitted infections (STI) and changes in the social determinants of health. An ecological study was conducted covering a five-year period (2018-2022), starting from the year of initiation of PrEP administration in Brazilian state capitals. PRINCIPAL FINDINGS: Descriptive analysis was performed, and the spatial distribution of study data was taken into account. Correlation analysis was used to assess the association between PrEP administration, the incidence and detection rate of STI, and socioeconomic data. The southern region showed the highest incidence rates of STI, but the northern and northeastern regions demonstrated the worst socioeconomic indicators, especially those related to illiteracy and basic sanitation. PrEP administration was significantly correlated with illiteracy (ρ = -0.658), per capita income (ρ = 0.622), public garbage collection (ρ = 0.612), syphilis (ρ = 0.628) and viral hepatitis (ρ = 0.419) incidences. Further, all STI were significantly associated with illiteracy and per capita income. SIGNIFICANCE: Our findings highlight the need to continue exploring PrEP use and rising syphilis rates. In terms of policy, PrEP administration appears to be inversely associated with regions of greater social vulnerability. Further efforts should focus on the social determinants and health needs of this population to improve access to PrEP and reduce social disparities.

Descemet's Membrane Endothelial Keratoplasty for Corneal Endothelial Failure Secondary to Three Types of Phakic Intraocular Lens - Retrospective Study.

Purpose: To analyze the outcomes of Descemet's membrane endothelial keratoplasty (DMEK) for corneal endothelial failure secondary to phakic intraocular lens implantation (PIOL) at a reference center for corneal transplantation in Spain. Design: Retrospective, single-surgeon case series. Methods: Single-center analysis of patients who underwent DMEK for PIOL-related corneal decompensation between July 2011 and July 2020 with at least 6 months of follow-up postoperatively. Primary outcome was final best-corrected visual acuity (BCVA, logMAR) compared to pre-DMEK BCVA. Secondary outcomes analyzed included post-DMEK refractive spherical equivalent, endothelial cell loss (%ECL), and graft failure. Results: Sixteen eyes (14 patients) underwent DMEK for PIOL-related corneal decompensation. Mean (SD) time to PIOL explantation was 9.3 (5.0) years, and median (P25-P75) time between PIOL explantation and DMEK surgery was 3 (2-4) months. Median pre-DMEK BCVA was 0.80 (1.08-0.60) logMAR. A statistically significant improvement in BCVA was observed 1 month after DMEK (p = 0.001), and median final BCVA was 0.15 (0.0-0.35) logMAR (p = 0.002). Mean %ECL was 55.6 (18.7) % at 2-year follow-up and 61.7 (11.7) % in eyes with over 4 years of follow-up. Two eyes required re-bubbling (12.5%), one of which ended in primary graft failure (6.2%) and one eye had late endothelial graft failure (LEGF) at 4-year follow-up (1/15 grafts, 6.7%). Conclusion: In patients with PIOL-related corneal decompensation, DMEK leads to good and clinically significant refractive and visual outcomes in the medium-long term, with a good safety profile. Prospective studies are encouraged to ascertain whether these cases are at increased risk of accelerated endothelial cell loss and LEGF.

Outcomes of cystoid macular edema following Descemet's membrane endothelial keratoplasty in a referral center for keratoplasty in Spain: retrospective study.

The aim of this study was to analyze the outcomes of eyes with visually significant cystoid macular œdema (vs-CMO) after Descemet membrane endothelial keratoplasty (DMEK) in a referral center for keratoplasty in Spain. We conducted a retrospective, single-surgeon case series of eyes that developed post-DMEK vs-CMO performed between January 2011 and December 2020. Data collected included: indication for DMEK; biometric data; ocular comorbidities; past medical history; time to detection of vs-CMO after DMEK (T, weeks); best-corrected visual acuity (BCVA, logMAR) and central retinal thickness (CRT, µm) at diagnosis of vs-CMO, after resolution of CMO, and at last follow-up; and management strategy. Main outcomes analyzed were incidence of vs-CMO, improvement in BCVA and CRT after treatment of vs-CMO. Of 291 consecutive DMEK surgeries, 14 eyes of 13 patients (4.8%) developed vs-CMO. Five patients (38.5%) had history of CMO, and 28.6% of eyes had ophthalmic comorbidities. Median (P25-P75) T was 4 (3-10) weeks. Treatment success was observed in 12/13 eyes (92.3%), two of which required second-line treatment. In successful cases (median time-to-resolution 3.0 (2.0-3.5) months), median BCVA improved from 0.60 (0.40-0.80) logMAR to 0.30 (0.15-0.40) logMAR (p = 0.002) after treatment, and median CRT improved from 582.5 (400.0-655.0) µm to 278.0 (258.0-294.0) µm (p = 0.005). In our study, we found a 4.8% rate of post-DMEK vs-CMO, with most cases occurring in the first 3 months after surgery. Good functional and anatomical outcomes are expected in most eyes, without treatment-related complications or implications in graft outcomes. Additional studies are encouraged to determine a standardized protocol for post-DMEK vs-CMO.

Photorefractive keratectomy after DMEK for corneal decompensation by phakic IOL.

PURPOSE: To provide the first description of photorefractive keratectomy (PRK) for the correction of mild residual refractive error after Descemet membrane endothelial keratoplasty (DMEK). METHODS: Case report. RESULTS: A 45 year-old woman presenting with phakic intraocular lens (PIOL)-related corneal decompensation underwent staged DMEK surgery following PIOL explantation and cataract surgery. Eighteen months after DMEK, uncorrected distance visual acuity (UDVA) was 20/60 and best-corrected visual acuity (BCVA) was 20/22, with a stable refraction. The patient requested refractive surgery to decrease spectacle dependance, and wavefront-optimized PRK was performed. At last follow-up observation thirty-three months after PRK (54 months after DMEK surgery), UDVA was 20/20, the cornea remained clear without signs of rejection or endothelial failure, and the endothelial cell loss rate was not accelerated after PRK. CONCLUSION: Since long-term visual and refractive stability can be expected after DMEK, PRK may be a particular safe and effective approach for the correction of mild residual refractive errors after DMEK. However, we consider that surgeons must exercise caution when considering keratorefractive surgery in these eyes due to postoperative changes in corneal curvature and thickness, and further studies are encouraged.

Corrigendum: Clinical 3-D gait assessment of patients with polyneuropathy associated with hereditary transthyretin amyloidosis.

[This corrects the article DOI: 10.3389/fneur.2020.605282.].

Towards a Closed-loop Neuro-Robotic Approach to DBS Electrode Implantation based on Real-Time Wrist Rigidity Evaluation.

The iHandU system is a wearable device that quantitatively evaluates changes in wrist rigidity during Deep Brain Stimulation (DBS) surgery, allowing clinicians to find optimal stimulation settings that reduce patient symptoms. Robotic accuracy is also especially relevant in DBS surgery, as accurate electrode placement is required to increase effectiveness and reduce side effects. The main goal of this work is to integrate the advantages of each system in a closed-loop system between an industrial robot and the iHandU system. For this purpose, a comparative analysis of a Leksell stereotactic frame and neuro-robotic system accuracies was performed using a lab-made phantom. The neuro-robotic system reached 90% of trajectories, while the stereotactic frame reached all trajectories. There are significant differences in accuracy errors between these trajectories (p < 0.0001), which can be explained by the high correlation between the neuro-robotic system errors and the distance from the trajectory to the origin of the Leksell coordinate system (ρ = 0.72). Overall accuracy is comparable to existing neuro-robotic systems, achieving a deviation of (1.0 ± 0.5) mm at the target point. The accuracy of DBS electrode positioning and stimulation parameters choice leads to better long-term clinical outcomes in Parkinson's disease patients. Our neuro-robotic system combines real-time feedback assessment of the patient's symptomatic response and automatic positioning of the DBS electrode in a specific brain area.

Gait Characterization and Analysis of Hereditary Amyloidosis Associated with Transthyretin Patients: A Case Series.

Hereditary amyloidosis associated with transthyretin (ATTRv), is a rare autosomal dominant disease characterized by length-dependent symmetric polyneuropathy that has gait impairment as one of its consequences. The gait pattern of V30M ATTRv amyloidosis patients has been described as similar to that of diabetic neuropathy, associated with steppage, but has never been quantitatively characterized. In this study we aim to characterize the gait pattern of patients with V30M ATTRv amyloidosis, thus providing information for a better understanding and potential for supporting diagnosis and disease progression evaluation. We present a case series in which we conducted two gait analyses, 18 months apart, of five V30M ATTRv amyloidosis patients using a 12-camera, marker based, optical system as well as six force platforms. Linear kinematics, ground reaction forces, and angular kinematics results are analyzed for all patients. All patients, except one, showed a delayed toe-off in the second assessment, as well as excessive pelvic rotation, hip extension and external transverse rotation and knee flexion (in stance and swing phases), along with reduced vertical and mediolateral ground reaction forces. The described gait anomalies are not clinically quantified; thus, gait analysis may contribute to the assessment of possible disease progression along with the clinical evaluation.

DMEK for the treatment of interface fluid syndrome secondary to failed DSAEK graft: A case report and review of the literature.

Purpose: To report a case of Descemet membrane endothelial keratoplasty (DMEK) for the management of post-laser in situ keratomileusis (LASIK) interface fluid syndrome (IFS) secondary to failed Descemet stripping automated endothelial keratoplasty (DSAEK) graft, and to provide a literature review on endothelial keratoplasty (EK) for this indication. Observations: A 52-year-old patient presented with LASIK interface fluid accumulation and a non-functioning primary DSAEK graft. Past ophthalmic history was relevant for: (1) phakic intraocular lens (PIOL) implantation with later refinement by LASIK; (2) combined PIOL explantation and refractive lens exchange due to accelerated endothelial cell loss (ECL); (3) primary DSAEK due to corneal decompensation.A secondary EK graft (DMEK) was performed, and the patient was prospectively followed for 6 months (M6). DMEK surgery was uneventful, without postoperative graft detachment. Corneal clearing and resolution of interface fluid accumulation occurred during the first postoperative month. Best-corrected visual acuity (BCVA) improved from 20/800 Snellen to 20/25 Snellen at 3-month follow-up, remaining stable at M6. Due to a persistent rise in intraocular pressure (IOP), the patient underwent uneventful non-penetrating deep sclerectomy 2 months after DMEK, with controlled IOP and without accelerated ECL. Conclusions and Importance: DMEK is feasible, effective, and safe in the management of IFS in cases where corneal endothelial failure plays a major role, even in complex eyes with previous EK grafts. Aggressive postoperative IOP control is warranted to decrease the risk of interface fluid recurrence and damage to the optic nerve. Studies with larger patient numbers are encouraged to ascertain the role of EK for this indication.

Clinical and Functional Results of Reverse Total Shoulder Arthroplasty and Postoperative Rehabilitation Protocol.

Purpose This retrospective study aims to analyze the clinical and functional results obtained over a seven-year period of performing reverse total shoulder arthroplasty (RTSA) and the subsequent postoperative rehabilitation protocol. Methods We analyzed data from 80 patients who were evaluated at a preoperative, as well as monthly postoperative outpatient consultation, until the discharge from the rehabilitation program, using Constant Score (CS). Results A comparison of preoperative and postoperative (after rehabilitation protocol) results revealed an improved functional score of absolute CS (20.8 increase), normal relative CS (29.1 increase), and individual relative CS (31.7 increase) with statistical significance (p<0.05). From the analysis of CS subscores, there was a positive evolution of the pain subscore, as well as flexion, abduction, and external rotation combined with abduction range of motion (ROM). Contrarily, there was a negative evolution of the combined internal rotation, extension, and adduction ROM, as well as deltoid muscle strength. No statistically significant correlations were found between age and postoperative CS, as well as between the time interval from surgery to the beginning of outpatient rehabilitation and CS evolution. Conclusion Our study demonstrates that RTSA is an effective therapeutic option that, if combined with a well-structured rehabilitation program, can improve pain, mobility, and upper limb functionality.

Magnitude of tuberculosis cases notified in a municipality: epidemiological profile and risk factors, a temporal description / Magnitude dos casos de tuberculose notificados em um município: perfil epidemiológico e fatores de risco, uma descrição temporal

Background: Tuberculosis remains among the most prevalent infectious diseases worldwide, Risk factors include sociodemographic factors and comorbidities such as alcohol consumption, diabetes mellitus, the use of legal and illegal drugs and HIV. This research aimed to estimate the incidence of tuberculosis cases and describe the epi-demiological profile of all tuberculosis cases reported to the National System of Notifiable Diseases in the city of Campo Grande/MS, correlating with national and international literature. Methods: This is a cross-sectional survey of secondary data that analyzed all cases reported in the city from January 2014 to December 2019. Results: There was a predominance of males (80.3%). The most affected age group corresponded to individuals of working age (20 to 59 years), with 84% of the total data. As for comorbidities, 70.5% had at least one. Smoking was the most prevalent health issue (27%), followed by the use of psychoactive substances, alcohol consumption and HIV/Aids co-infection (13.8%). Diabetes was the lowest rated disease, with 5,4%. Conclusions: The data obtained points to the need to assess the directly observed treatment (DOT) in the capital, given the alarming rate of adherence od 3.8%. About one third of tuberculosis cases were diagnosed in hospitals, supporting the hypothesis of delayed diagnosis, which leverages the need for health actions on the subject (AU)

ntrodução: A tuberculose permanece entre as doenças infecciosas mais prevalentes em todo o mundo, os fatores de risco incluem fatores sociodemográficos e comorbidades como consumo de álcool, diabetes mellitus, uso de dro-gas lícitas e ilícitas e HIV. Esta pesquisa teve como objetivo estimar a incidência de casos de tuberculose e descrever o perfil epidemiológico de todos os casos notificados ao Sistema Nacional de Agravos de Notificação do município de Campo Grande/MS, correlacionando com a literatura nacional e internacional. Métodos: Trata-se de um levanta-mento transversal de dados que analisou todos os casos notificados em um período de 6 anos. Resultados: Houve predomínio do sexo masculino (80,3%). A faixa etária mais acometida correspondeu aos indivíduos em idade ativa (20 a 59 anos), com 84% do total de dados. O tabagismo foi o problema de saúde mais prevalente (27%), seguido pelo uso de substâncias psicoativas, alcoolismo e coinfecção HIV/Aids. Conclusões: Os dados obtidos apontam para a necessidade de avaliar o tratamento diretamente observado (TDO) na capital, dada a alarmante taxa de adesão. Cerca de 33% dos casos de tuberculose foram diagnosticados em hospitais, corroborando a hipótese de diagnóstico tardio, a qual alavanca a necessidade de ações de saúde sobre a temática (AU)

Mortalidade infantil em menores de cinco anos em um hospital público de Campo Grande/MS: uma descrição temporal / Mortalidad infantil en menores de cinco años en un hospital público de Campo Grande / MS: descripción temporal / Infant mortality in children under five years old in a public hospital in Campo Grande/MS: a temporal description

Objetivos: identificar a causa de morte infantil hospitalar, correlacionando-a com as causas evitaveís de mortalidade e associando-a com a prevalência do município. Métodos: a pesquisa foi realizada utilizando como base de informações as certidões de óbitos e prontuários arquivados no Hospital Regional do Mato Grosso do Sul, dos quais foram selecionados os óbitos do período de 2012 a 2017 de crianças menores de 5 anos e foram analisados as variáveis sociodemográficas e causas das mortes. Resultados: ocorreram 364 mortes infantis no período, sendo que 75% dos óbitos registrados são classificados como causas evitáveis de óbitos infantis. Conclusão: são necessárias ações para a qualificação de recursos humanos e estruturas de saúde no âmbito hospitalar com enfoque nas causas evitáveis, sendo mandatório a atualização dos indicadores de mortalidade infantil, visto que representam a efetividade dos serviços de saúde e fazem parte da vigilância epidemiologia no âmbito da saúde coletiva.(AU)

Objectives: to identify the cause of infant death in hospital, correlating it with preventable causes of mortality and associating it with the prevalence in the municipality. Methods: the research was conducted using death certificates and medical records filed at the Regional Hospital of Mato Grosso do Sul as a basis of information, from which deaths from 2012 to 2017 of children under 5 years were selected and the variables were analyzed sociodemographic factors and causes of death. Results: there were 364 infant deaths in the period, and 75% of registered deaths are classified as preventable causes of infant deaths. Conclusion: actions are needed for the qualification of human resources and health structures in the hospital environment with a focus on preventable causes, and it is mandatory to update the infant mortality indicators, as they represent the effectiveness of health services and are part of the epidemiology surveillance in the scope of collective health.(AU)

Objetivos: identificar la causa de muerte infantil en el hospital, correlacionarla con las causas prevenibles de mortalidad y asociarla con la prevalencia en el municipio. Métodos: la investigación se realizó utilizando como base de información los certificados de defunción y las historias clínicas archivadas en el Hospital Regional de Mato Grosso do Sul, a partir de la cual se seleccionaron las defunciones de 2012 a 2017 de niños menores de 5 años y se analizaron las variables factores sociodemográficos y causas de muerte. Resultados: hubo 364 defunciones infantiles en el período y el 75% de las defunciones registradas se clasifican como causas evitables de defunción infantil. Conclusión: se requieren acciones para la calificación de los recursos humanos y las estructuras de salud en el ámbito hospitalario con foco en las causas prevenibles, y es obligatorio actualizar los indicadores de mortalidad infantil, ya que representan la efectividad de los servicios de salud y son parte de la epidemiología vigilancia en el ámbito de la salud colectiva(AU)

New highly antigenic linear B cell epitope peptides from PvAMA-1 as potential vaccine candidates.

Peptide-based vaccines have demonstrated to be an important way to induce long-lived immune responses and, therefore, a promising strategy in the rational of vaccine development. As to malaria, among the classic vaccine targets, the Apical membrane antigen (AMA-1) was proven to have important B cell epitopes that can induce specific immune response and, hence, became key players for a vaccine approach. The peptides selection was carried out using a bioinformatic approach based on Hidden Markov Models profiles of known antigens and propensity scale methods based on hydrophilicity and secondary structure prediction. The antigenicity of the selected B-cell peptides was assessed by multiple serological assays using sera from acute P.vivax infected subjects. The synthetic peptides were recognized by 45.5%, 48.7% and 32.2% of infected subjects for peptides I, II and III respectively. Moreover, when synthetized together (tripeptide), the reactivity increases up to 62%, which is comparable to the reactivity found against the whole protein PvAMA-1 (57%). Furthermore, IgG reactivity against the tripeptide after depletion was reduced by 42%, indicating that these epitopes may be responsible for a considerable part of the protein immunogenicity. These results represent an excellent perspective regarding future chimeric vaccine constructions that may come to contemplate several targets with the potential to generate the robust and protective immune response that a vivax malaria vaccine needs to succeed.

The gene repertoire of the main cysteine protease of Trypanosoma cruzi, cruzipain, reveals four sub-types with distinct active sites.

Cruzipains are the main papain-like cysteine proteases of Trypanosoma cruzi, the protozoan parasite that causes Chagas disease. Encoded by a multigenic family, previous studies have estimated the presence of dozens of copies spread over multiple chromosomes in different parasite strains. Here, we describe the complete gene repertoire of cruzipain in three parasite strains, their genomic organization, and expression pattern throughout the parasite life cycle. Furthermore, we have analyzed primary sequence variations among distinct family members as well as structural differences between the main groups of cruzipains. Based on phylogenetic inferences and residue positions crucial for enzyme function and specificity, we propose the classification of cruzipains into two families (I and II), whose genes are distributed in two or three separate clusters in the parasite genome, according with the strain. Family I comprises nearly identical copies to the previously characterized cruzipain 1/cruzain, whereas Family II encompasses three structurally distinct sub-types, named cruzipain 2, cruzipain 3, and cruzipain 4. RNA-seq data derived from the CL Brener strain indicates that Family I genes are mainly expressed by epimastigotes, whereas trypomastigotes mainly express Family II genes. Significant differences in the active sites among the enzyme sub-types were also identified, which may play a role in their substrate selectivity and impact their inhibition by small molecules.

Supporting the Assessment of Hereditary Transthyretin Amyloidosis Patients Based On 3-D Gait Analysis and Machine Learning.

Hereditary Transthyretin Amyloidosis (vATTR-V30M) is a rare and highly incapacitating sensorimotor neuropathy caused by an inherited mutation (Val30Met), which typically affects gait, among other symptoms. In this context, we investigated the possibility of using machine learning (ML) techniques to build a model(s) that can be used to support the detection of the Val30Met mutation (possibility of developing the disease), as well as symptom onset detection for the disease, given the gait characteristics of a person. These characteristics correspond to 24 gait parameters computed from 3-D body data, provided by a Kinect v2 camera, acquired from a person while walking towards the camera. To build the model(s), different ML algorithms were explored: k-nearest neighbors, decision tree, random forest, support vector machines (SVM), and multilayer perceptron. For a dataset corresponding to 66 subjects (25 healthy controls, 14 asymptomatic mutation carriers, and 27 patients) and several gait cycles per subject, we were able to obtain a model that distinguishes between controls and vATTR-V30M mutation carriers (with or without symptoms) with a mean accuracy of 92% (SVM). We also obtained a model that distinguishes between asymptomatic and symptomatic carriers with a mean accuracy of 98% (SVM). These results are very relevant, since this is the first study that proposes a ML approach to support vATTR-V30M patient assessment based on gait, being a promising foundation for the development of a computer-aided diagnosis tool to help clinicians in the identification and follow-up of this disease. Furthermore, the proposed method may also be used for other neuropathies.

Clinical 3-D Gait Assessment of Patients With Polyneuropathy Associated With Hereditary Transthyretin Amyloidosis.

Hereditary amyloidosis associated with transthyretin V30M (ATTRv V30M) is a rare and inherited multisystemic disease, with a variable presentation and a challenging diagnosis, follow-up and treatment. This condition entails a definitive and progressive motor impairment that compromises walking ability from near onset. The detection of the latter is key for the disease's diagnosis. The aim of this work is to perform quantitative 3-D gait analysis in ATTRv V30M patients, at different disease stages, and explore the potential of the obtained gait information for supporting early diagnosis and/or stage distinction during follow-up. Sixty-six subjects (25 healthy controls, 14 asymptomatic ATTRv V30M carriers, and 27 symptomatic patients) were included in this case-control study. All subjects were asked to walk back and forth for 2 min, in front of a Kinect v2 camera prepared for body motion tracking. We then used our own software to extract gait-related parameters from the camera's 3-D body data. For each parameter, the main subject groups and symptomatic patient subgroups were statistically compared. Most of the explored gait parameters can potentially be used to distinguish between the considered group pairs. Despite of statistically significant differences being found, most of them were undetected to the naked eye. Our Kinect camera-based system is easy to use in clinical settings and provides quantitative gait information that can be useful for supporting clinical assessment during ATTRv V30M onset detection and follow-up, as well as developing more objective and fine-grained rating scales to further support the clinical decisions.

Synergistic effects of binary mixtures of linalool with pyrethroids against fall armyworm / Efeitos sinérgicos de misturas binárias de linalol com piretroides contra lagarta-do-cartucho

The present work aimed to determine the toxicity of linalool and evaluate the lethal and toxic effects of linalool associated with pyrethroids in binary mixtures to fall armyworm (Spodoptera frugiperda). The insects used in the experiment were obtained from stock breeding initiated from larvae collected from conventional corn plants, grown in an experimental area, in the city of Uberlândia, Minas Gerais. Also, it was obtained essential oil from a variety of Ocimum basilicum, with a high content of linalool (80%), found naturally, as a measure of comparison of different linalool (97.5%) assays. Dose-response bioassays with 3rd instar larvae were performed to determine lethal dose for 50% mortality (LD50) of linalool. Toxicity tests were also performed with O. basilicum essential oil and with pyrethroid insecticides: deltamethrin and its commercial product (Decis 25 EC, Bayer®). After this, combinations between different doses of these products were made and applied on 3rd instar larvae of Spodoptera frugiperda (Smith). Linalool presented high toxicity to S. frugiperda (LD50 = 0.177 µL a.i. µL-1). It was observed neurotoxic effects after the linalool application since the insects presented an aspect of confusion, followed by extreme agitation and finally death. All binary mixtures caused mortality higher than the products applied alone (deltamethrin and linalool) used at 100% LD50, except to 75% LD50 deltamethrin added to 25% LD50 linalool, whose mortality did not differ the products alone, in 24 hours. It was obtained over 90% larval mortality when linalool was combined with 25% LD50 of deltamethrin, in 24 and 48 hours after application, and over 80% of mortality when linalool was combined with 25% LD50 of Decis, only in 48 hours after application. We conclude that linalool is a potential insecticidal and can be associated with pyrethroids to control of S. frugiperda. Further studies are required in order to evaluate the synergistic combinations against field populations of S. frugiperda.

O objetivo deste trabalho foi determinar a toxicidade do linalol e avaliar os efeitos tóxicos e letais do linalol associado a piretroides em misturas binárias para lagarta do cartucho do milho (Spodoptera frugiperda). Os insetos utilizados no experimento foram obtidos de criação estoque iniciada a partir de larvas coletadas em plantas de milho convencional, cultivado em área experimental, no município de Uberlândia, Minas Gerais. Também foi obtido óleo essencial de uma variedade de Ocimum basilicum, com alto teor de linalol (80%), encontrado naturalmente, como medida de comparação para ensaios com linalol (97.5%). Os bioensaios do tipo dose-resposta com larvas de 3º instar foram realizados para determinar a dose letal do linalol para 50% de mortalidade da população (DL50). Também foram realizados testes de toxicidade com óleo essencial de Ocimum basilicum e com inseticidas piretroides: deltametrina e seu produto comercial (Decis 25 EC, Bayer®). Em seguida, foram realizadas combinações entre diferentes doses desses produtos e aplicadas em larvas de 3º instar de Spodoptera frugiperda (Smith). De acordo com os resultados, observou-se que o linalol apresentou alta toxicidade para S. frugiperda (DL50 = 0,177 µL a. i. µL-1). Foram observados efeitos neurotóxicos após a aplicação do linalol, uma vez que os insetos apresentaram um aspecto de confusão, seguido de extrema agitação e, por fim, morte. Todas as combinações binárias causaram mortalidade maior que os produtos aplicados isoladamente (deltametrina e linalol) utilizando-se 100% da DL50, exceto para 75% DL50 de deltametrina somada a 25% DL50 de linalol, cuja mortalidade não diferiu dos produtos isolados, em 24 horas após a aplicação. Foi obtida mais de 90% de mortalidade de larvas quando se combinou linalol com 25% da DL50 de deltametrina, em 24 e 48 horas após a aplicação, e mais de 80% de mortalidade quando se combinou linalol com 25% da DL50 do produto comercial, somente 48 horas após a aplicação. Concluímos que o linalol é um potencial inseticida e pode ser associado a piretroides no controle de S. frugiperda. Mais estudos são necessários em vista de avaliar as combinações sinérgicas contra populações de campo de S. frugiperda.

Author Correction: iLoF: An intelligent Lab on Fiber Approach for Human Cancer Single-Cell Type Identification.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Optic neuropathy due to chronic lymphocytic leukemia: The first manifestation of the disease.

PURPOSE: Chronic lymphocytic leukemia (CLL) is the most common lymphoproliferative disorder in the western world. The involvement of the central nervous system (CNS) or the optic nerve in CLL, however, is rare. We report a case of a previously untreated patient with CLL whose first manifestation of the disease was a progressive visual loss caused by optic neuropathy. OBSERVATIONS: Clinical manifestations, optical coherence tomography (OCT), and automated visual fields pointed to the diagnosis of neuropathy. Leukemic involvement of the CNS was confirmed after cells suggestive of CLL were found by cerebrospinal fluid analysis. Optic nerve infiltration is thought to be the cause of this optic neuropathy, and the clinical course and treatment are described herein. CONCLUSIONS: When readily diagnosed, optic nerve infiltration is a rare, yet manageable complication of CLL.