Impact of Comorbid Sleep-Disordered Breathing and Atrial Fibrillation on the Long-Term Outcome After Ischemic Stroke.

BACKGROUND: Sleep-disordered breathing (SDB) and atrial fibrillation (AF) are highly prevalent in patients with stroke and are recognized as independent risk factors for stroke. Little is known about the impact of comorbid SDB and AF on long-term outcomes after stroke. METHODS: In this prospective cohort study, 353 patients with acute ischemic stroke or transient ischemic attacks were analyzed. Patients were screened for SDB by respiratory polygraphy during acute hospitalization. Screening for AF was performed using a 7-day ECG up to 3× in the first 6 months. Follow-up visits were scheduled at 1, 3, 12, 24, and 36 months poststroke. Cox regression models adjusted for various factors (age, sex, body mass index, hypertension, diabetes, dyslipidemia, and heart failure) were used to assess the impact of comorbid SDB and AF on subsequent death or cerebro-cardiovascular events. RESULTS: Among 353 patients (299 ischemic stroke and 54 transient ischemic attacks), median age, 67 (interquartile range, 57-74) years with 63% males. Moderate-to-severe SDB (apnea-hypopnea index score, ≥15/h) was present in 118 (33.4%) patients. Among the 56 (15.9%) patients with AF, 28 had comorbid moderate-to-severe SDB and AF. Over 36 months, there were 12 deaths and 67 recurrent cerebro-cardiovascular events. Patients with comorbid moderate-to-severe SDB and AF had a higher risk of subsequent death or cerebro-cardiovascular events compared with those with only moderate-to-severe SDB without AF (hazard ratio, 2.49 [95% CI, 1.18-5.24]) and to those without moderate-to-severe SDB or AF (hazard ratio, 2.25 [95% CI, 1.12-4.50]). However, no significant difference was found between the comorbid moderate-to-severe SDB and AF group and the group with only AF without moderate-to-severe SDB (hazard ratio, 1.64 [95% CI, 0.62-4.36]). CONCLUSIONS: Comorbid moderate-to-severe SDB and AF significantly increase the risk of long-term mortality or recurrent cerebro-cardiovascular events after acute ischemic stroke. Considering both conditions as cumulative and modifiable cerebro-cardiovascular risk factors is of interest for the management of acute stroke. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02559739.

People living with HIV co-infected with the Kaposi Sarcoma-associated Herpes Virus have a distinct HIV Tat profile and higher rates of antiretroviral virologic failure, more evident among those with Kaposi's sarcoma.

Kaposi sarcoma (KS) is a neoplasm of vascular origin that promotes angiogenesis and the growth of endothelial cells triggered by the Kaposi Sarcoma-associated Herpes Virus (KSHV). When associated with HIV, KSHV becomes more aggressive and rapidly evolves. The HIV-1 TAT protein can be essential in developing AIDS-associated KS by promoting angiogenesis and increasing KSHV replication. Therefore, we evaluated the genetic profile of the first exon of tat gene among groups of people living with HIV (PLHIV) with (case group, n = 36) or without KS, this later with (positive control group, n = 46) and without KSHV infection (negative control group, n = 24); all individuals under antiretroviral therapy. The genetic diversity, the DN/DS ratio, and the genetic entropy of the first exon of tat were higher in the case group, followed by the positive control group, which was higher than the negative control group. The number of tat codons under positive selection was seven in the case group, six in the positive control group, and one in the negative control group. The prevalence of HIV viral loads below the detection limit was equal in the case and positive control groups, which were lower than in the negative control group. The mean CD4+ T cell counts were higher in the negative control group, followed by the positive control group, and followed by the case group. These results emphasize the negative influence of KSHV in antiretroviral treatment, as well as the HIV-specific TAT profile among PLHIV who developed KS.

Early sleep apnea treatment in stroke (eSATIS) - a multicentre, randomised controlled, rater-blinded, clinical trial: The association of post-stroke cognition with sleep-disordered breathing and its treatment.

Sleep-disordered breathing (SDB) is linked to cognitive dysfunction. Although SDB is common in stroke patients, the impact of SDB and its early treatment on cognitive functioning after stroke remains poorly investigated. Therefore, we explored the association between SDB and post-stroke cognitive functioning, including the impact of early SDB treatment with adaptive servo-ventilation (ASV) on cognitive recovery from acute event to 3 months post-stroke. We used data from two studies, which included ischaemic stroke patients (n = 131) and no-stroke controls (n = 37) without SDB (apnea-hypopnea index, AHI <5/h) and with SDB (AHI≥20/h). Cognitive functioning was assessed within 7 days and 3 months post-stroke in stroke patients, or at study inclusion in no-stroke control group, respectively. Stroke patients with SDB were randomized to ASV treatment (ASV+) or usual care (ASV-). Linear regression adjusted for main confounders assessed the impact of SDB and its treatment on cognitive recovery. The intention-to-treat analysis did not show significant associations of SDB ASV+ (n = 30) versus SDB ASV- (n = 29) with cognitive recovery. In an exploratory subanalysis, compliant SDB ASV+ (n = 14) versus SDB ASV- showed improvements with ASV in visual memory and cognitive flexibility. Combining the stroke and non-stroke datasets, SDB (n = 85) versus no-SDB (n = 83) was associated with deficits in visual memory and response inhibition independently of stroke. SDB ASV- versus no-SDB (n = 51) was associated with less improvement in visual memory. There was no substantial evidence for benefits of intention-to-treat ASV on cognitive recovery. Exploratory analysis indicated that compliant ASV treatment could benefit visual memory and cognitive flexibility, whereas untreated SDB could contribute to a poor recovery of visual memory.

Renal angina index for early identification of risk of acute kidney injury in critically ill children.

BACKGROUND: The main objective was to test whether the Renal Angina Index (RAI), calculated on patient admission to the pediatric intensive care unit (PICU), is associated with the risk of acute kidney injury (AKI) based on the Kidney Disease: Improving Global Outcomes (KDIGO) (stage ≥ 2) in 72 h. The specific aim was to analyze the performance of the RAI at a specialized oncology PICU. METHODS: Retrospective cohort study involving two pediatric intensive care units located within a general hospital and an oncology hospital. Children aged ≥ 3 months to < 18 years admitted to the intensive care units in 2017 with a length of stay ≥ 72 h were included. RESULTS: The sample included 249 patients, of which 51% were male (127 patients), with median age of 77 months, and mean ICU stay of 5 days. Of the total admissions, 141 were clinical (57%) and 108 surgical. The rate of AKI was 15% and death rate within 30 days was 13%. Having a positive RAI on admission showed a statistically significant association with AKI at Day 3 (OR = 18.5, 95%CI = 4.3 - 78.9, p < 0.001) and with death (OR = 3.9, 95%CI = 1.6 - 9.9, p = 0.004). The accuracy of the RAI in the cancer population was 0.81 on the ROC curve (95%CI 0.74, 0.88). CONCLUSIONS: The RAI is a useful tool for predicting AKI and death in critically ill children, including in oncology units.

Early Candida colonisation impact on patients and healthcare professionals in an intensive care unit.

OBJECTIVES: Candida spp. is an opportunistic pathogen that causes superficial and invasive infections with nosocomial outbreaks without strict hygiene protocols. Herein, we assessed oral colonisation by Candida spp. in 209 Intensive Care Unit (ICU) patients between July 2021 and April 2022, conducting clinical, epidemiological, and microbiological characterisation of those developing oral or invasive candidiasis. METHODS: Initial oral swabs were collected within 24 h of admission in the ICU, followed by collections on Days 2, 4, 6 and 8. Swabs from denture-wearing patients, abiotic surfaces, healthcare professionals' hands, and retroauricular regions were also obtained. Recovered yeasts and filamentous fungi were identified using MALDI-TOF MS and morphological characteristics, respectively. Genetic similarity of Candida spp. isolates was evaluated using Amplified fragment length polymorphism (AFLP), and the antifungal susceptibility profile was determined by broth microdilution. RESULTS: In the study, 64.11% of patients were orally colonised by Candida spp. Of these, 80.59% were colonised within the first 24 h. Oral colonisation also occurred on subsequent days: 50%/Day 2, 26.92%/Day 4, and 11.53%/Days 6 and 8. Of the patients, 8.61% had oral candidiasis, mainly pseudomembranous. Among orally colonised patients, 2.23% developed invasive candidiasis. Besides, 89.47% of healthcare professionals evaluated were colonised. MALDI-TOF MS identified different yeast species, and C. albicans (45.34%), C. tropicalis (15.7%), and C. parapsilosis sensu stricto (9.88%) were the most prevalent. AFLP analysis indicated a high genetic correlation (≥97%) between C. parapsilosis sensu stricto isolates from patients and professionals. Three resistant C. albicans isolates were also found. CONCLUSION: This study reported a diversity of yeast and filamentous fungi species in ICU patients and highlighted early Candida spp. colonisation risks for invasive candidiasis, as well as the potential horizontal transmission in the nosocomial setting, emphasising the need for effective infection control measures.

Trivalent chromium isotopes in the eastern tropical North Pacific oxygen-deficient zone.

Changes in chromium (Cr) isotope ratios due to fractionation between trivalent [Cr(III)] and hexavalent [Cr(VI)] are being utilized by geologists to infer oxygen conditions in past environments. However, there is little information available on Cr in the modern ocean to ground-truth these inferences. Transformations between the two chromium species are important processes in oceanic Cr cycling. Here we present profiles of hexavalent and trivalent Cr concentrations and stable isotope ratios from the eastern tropical North Pacific (ETNP) oxygen-deficient zone (ODZ) which support theoretical and experimental studies that predict that lighter Cr is preferentially reduced in low-oxygen environments and that residual dissolved Cr becomes heavier due to removal of particle-reactive Cr(III) on sinking particles. The Cr(III) maximum dominantly occurs in the upper portion of the ODZ, implying that microbial activity (dependent on the sinking flux of organic matter) may be the dominant mechanism for this transformation, rather than a simple inorganic chemical conversion between the species depending on the redox potential.

Gastrointestinal release site for delayed release and gelatin capsules in healthy dogs.

Gelatin capsules deliver their contents to the stomach, while delayed-release (DR) capsules are designed to allow delivery to the small intestine. This study evaluated the gastrointestinal release site of DR capsules in six healthy adult dogs compared to gelatin capsules. Both gelatin and DR capsules were filled with barium-impregnated polyethylene spheres (BIPS™), and following enteral administration, release site was assessed using abdominal radiographs at baseline, immediately after ingestion, 15 min post-ingestion, 30 min post-ingestion, and then every 30 min thereafter. The evaluated phases included fasted conditions (phase 1, n = 6), increased meal size (phase 2, n = 2), double encapsulation (phase 3, n = 2), and altered capsule size (phase 4, n = 1). The released site was the stomach in all phases for both capsule types. In phase 1, DR capsules had a significantly prolonged time (median 60 min, range 60-90) to release BIPS™ compared to gelatin capsules (15 min, range 15-30; p = .03). In phase 2 (full meal size), 3 (double encapsulation), and 4 (smaller capsule size) pilot studies, release time was prolonged but still occurred in the stomach. This is similar to the release site for gelatin capsules but differs from the release site for DR capsules in people. This has implications for pharmacologic outcomes for products that are affected by gastric physiology (e.g. fecal microbiota transplantation). Based on this pilot data, clinicians and researchers should not assume DR capsules will allow for intestinal delivery of contents in dogs. Future studies should be conducted on larger and varied populations of dogs.

Cosmetic application of the stem-bark extract of Bertholletia excelsa H.B.K.

OBJECTIVE: The Amazon has a rich biodiversity where many different plant species can be found. This diversity is an important source of bioactive substances, mainly due to the different structural components of their phytometabolites. Research for natural products is a strategy for the development of new agents in therapeutic applications, especially cosmetic applications, that have better pharmacological potential. Within this perspective, the objective of the study was to investigate the cosmetic application (anti-aging potential) of the stem-bark extract of Bertholletia excelsa H.B.K - (SBEBE), popularly known as the Brazil nut tree, here called SBEBE, a noble plant species of the Amazon that is rich in selenium. METHODS: Enzymatic, glycation, proliferation, cell-healing, collagen quantification, toxicity and genotoxicity assays were used. RESULTS: Among the enzymes involved in the extracellular matrix of the skin, SBEBE was able to inhibit only elastase (62.67 ± 3.75) when compared to the standard sivelestat (89.04 ± 0.53), and the extract was also able to inhibit both the oxidative and the non-oxidative pathway. When cell toxicity in fibroblasts (MRC-5) and keratinocytes (HACAT) was evaluated, SBEBE did not present toxicity in 24 h of incubation. After this period, the extract showed average cytotoxicity in 48 and 72 h, but not enough to reach the concentration of 50% of MRC-5 fibroblasts. In the trypan blue assay, the extract promoted fibroblast proliferation in 24, 48 and 72 h of incubation, which was evaluated through exponential cell growth, with emphasis mainly on the lowest concentration with results higher than the standard. When the cell healing capacity was evaluated, in 48 h of exposure to fibroblast, SBEBE was able to induce a cell carpet (cell film) in the cell monolayer scratch assay. CONCLUSIONS: SBEBE stimulated collagen production at all concentrations tested. In the alkaline comet assay, at the lowest concentration, the extract did not induce DNA damage when compared to the reference drug doxorubicin. This study proved that SBEBE extract can be considered an ally in the treatment of skin anti-ageing as a possible biotechnological, phytocosmetic product.

OBJECTIF: L'Amazonie possède une riche biodiversité ou l'on trouve de nombreuses espèces végétales différentes. Cette diversité constitue une source importante de substances bioactives, principalement en raison des différents composants structurels de leurs phytométabolites. La recherche de produits naturels est une stratégie de développement de nouveaux agents à applications thérapeutiques, notamment cosmétiques, présentant un meilleur potentiel pharmacologique. Dans cette perspective, l'objectif de l'étude était d'étudier l'application cosmétique (potentiel anti­âge) de l'extrait d'écorce de tige de Bertholletia excelsa H.B.K ­ (SBEBE), communément connu sous le nom de noix du Brésil, ici appelé SBEBE, un arbre noble, espèce végétale d'Amazonie riche en sélénium. MÉTHODES: Des tests enzymatiques, de glycation, de prolifération, de guérison cellulaire, de quantification du collagène, de toxicité et de génotoxicité ont été utilisés. RÉSULTATS: Parmi les enzymes impliquées dans la matrice extracellulaire de la peau, le SBEBE était capable d'inhiber uniquement l'élastase (62,67 +­ 3,75) par rapport au sivelestat standard (89,04 +­ 0,53), et l'extrait était également capable d'inhiber à la fois la voie oxydative et non­oxydative. Lorsque la toxicité cellulaire dans les fibroblastes (MRC­5) et les kératinocytes (HACAT) a été évaluée, SBEBE n'a présenté aucune toxicité en 24 heures d'incubation. Après cette période, l'extrait a montré une cytotoxicité moyenne en 48 et 72 h, mais pas suffisamment pour atteindre la concentration de 50 % de fibroblastes MRC­5. Dans le test au bleu trypan, l'extrait a favorisé la prolifération des fibroblastes en 24, 48 et 72 heures d'incubation, qui a été évaluée par une croissance cellulaire exponentielle, en mettant l'accent principalement sur la concentration la plus faible avec des résultats supérieurs à la norme. Lorsque la capacité de guérison cellulaire a été évaluée, en 48 heures d'exposition aux fibroblastes, SBEBE a pu induire un tapis cellulaire (film cellulaire) dans le test de grattage de la monocouche cellulaire. CONCLUSIONS: SBEBE a stimulé la production de collagène à toutes les concentrations testées. Dans le test alcalin des comètes, à la concentration la plus faible, l'extrait n'a pas induit de dommages à l'ADN par rapport au médicament de référence, la doxorubicine. Cette étude a prouvé que l'extrait de SBEBE peut être considéré comme un allié dans le traitement anti­âge cutané en tant que possible produit biotechnologique et phytocosmétique.

Multiple sleep-wake disturbances after stroke predict an increased risk of cardio-cerebrovascular events or death: A prospective cohort study.

BACKGROUND AND PURPOSE: Contradictory evidence on the impact of single sleep-wake-disturbances (SWD), such as sleep-disorderd breating (SDB) or insomnia, in patients with stroke, on the risk of subsequent cardio- and cerebrovascular events (CCE) and death, exists. Very recent studies in the general population suggest that the presence of multiple SWD increases cardio-cerebrovascular risk. Hence, the aim of this study was to asssess whether a novel score capturing the burden of multiple SWD, a so called "sleep burden index", is predictive for subsequent CCE including death in a prospectively followed cohort of stroke patients. METHODS: Patients with acute ischemic stroke or transient ischemic attack (TIA) were prospectively recruited. Four SWD were analyzed: (i) SDB with respirography; (ii) insomnia (defined using the insomnia severity index [ISI]); (iii) restless legs syndrome (RLS; defined using the International RLS Study Group rating scale); and (iv) self-estimated sleep duration at 1 and 3 months. A "sleep burden index", calculated using the mean of z-transformed values from assessments of these four SWD, was created. The occurrence of CCE was recorded over a mean ± standard deviation (SD) follow-up of 3.2 ± 0.3 years. RESULTS: We assessed 437 patients (87% ischemic stroke, 13% TIA, 64% males) with a mean ± SD age of 65.1 ± 13.0 years. SDB (respiratory event index ≥ 5/h) was present in 66.2% of these patients. Insomnia (ISI ≥ 10), RLS and extreme sleep duration affected 26.2%, 6.4% and 13.7% of the patients 3 months post-stroke. Seventy out of the 437 patients (16%) had at least one CCE during the follow-up. The sleep burden index was associated with a higher risk for subsequent CCE, including death (odds ratio 1.80 per index unit, 95% confidence interval 1.19-2.72; p = 0.0056). CONCLUSION: The presence of multiple SWDs constitutes a risk for subsequent CCE (including death) within the first 3 years following stroke. Larger systematic studies should assess the utility of the sleep burden index for patients' risk stratification in clinical practice.

Characterization of mammary pathogenic Escherichia coli reveals the diversity of Escherichia coli isolates associated with bovine clinical mastitis in Brazil.

Mammary pathogenic Escherichia coli (MPEC) is one of the most common pathogens associated with clinical mastitis. We analyzed isolates obtained from milk samples of cows with clinical mastitis, collected from 10 farms in Brazil, to verify molecular and phenotypic characteristics. A total of 192 (4.5%) mammary pathogenic E. coli isolates were obtained from 4,275 milk samples analyzed, but we tested 161. We assigned most of these isolates to E. coli phylogroups B1 (52.8%) and A (36.6%), although phylogroups B2, C, D, E, and unknown also occurred. All isolates were assessed for the presence of several genes encoding virulence factors, such as adhesins (sfaDE, papC, afaBC III, ecpA, fimH, papA, and iha), toxins (hlyA, cnf1, sat, vat, and cdt), siderophores (iroN, irp2, iucD, ireA, and sitA), an invasion protein (ibeA), and serum resistance proteins (traT, KpsMTII, and ompT), and isolates from phylogroups B1, B2, and E showed up to 8 genes. Two isolates harbored the locus of enterocyte effacement (escN+) and lack the bundle-forming pilus (bfpB-) operon, which corresponds to a molecular profile of a subgroup of diarrheagenic E. coli (aEPEC), thus being classified as hybrid MPEC/aEPEC isolates. These isolates displayed a localized adherence-like pattern of adherence in HeLa cells and were able to promote F-actin polymerization underneath adherent bacteria. Based on the pulsed-field gel electrophoresis analyses, considerable genetic variability was observed. A low index of antimicrobial resistance was observed and 2 extended-spectrum ß-lactamase-producing E. coli were identified, both harboring blaCTX-M15 gene, and were classified as ST10 and ST993 using multilocus sequence typing. A total of 148 (91.2%) isolates were weak biofilm producers or formed no biofilm. Because raw milk is still frequently consumed in Brazil, the occurrence of virulence factor-encoding genes from extraintestinal or diarrheagenic E. coli added to the presence of extended-spectrum ß-lactamase-producing isolates can turn this veterinary medicine problem into a public health concern.

Adjustable-loop implants are non-inferior to fixed-loop implants for femoral fixation in anterior cruciate ligament reconstruction.

PURPOSE: Button implants with an adjustable-loop device (ALD) are often used in anterior cruciate ligament reconstruction (ACLR). Clinical research comparing ALDs with fixed-loop devices (FLD) has mainly been conducted in small patient populations with short follow-up times. To determine whether ALDs are safe to use in ACLR, a non-inferiority study with a large sample population and a long follow-up period would be beneficial. This study compared ALDs with FLDs to determine non-inferior revision surgery rates, knee stability, and patient-reported outcomes (PROM) in ACLRs. METHODS: This non-inferiority register-based cohort study was conducted using data from the Danish Knee Ligament Reconstruction Registry (DKRR). A total of 12,723 patients > 15 years of age with primary ACLR using hamstring tendon autografts and either an FLD or ALD for femoral fixation were included: 9719 patients were in the FLD group, and 3014 patients were in the ALD group. The primary outcome was revision ACLR with a non-inferiority margin for ALDs at 4% at the 2-year follow-up. The secondary outcomes were anterior and rotatory knee stability and PROMs based on the Knee Injury and Osteoarthritis Outcome Score (KOOS) at the 1-year follow-up. RESULTS: The crude cumulative revision rates in ALD implants at 2 and 5 years were 2.1% (95% CI 1.62-2.68) and 5.0% (95% CI 4.22-5.96), respectively. In the FLD group, the rates were 2.2% (95% CI 1.89-2.48) at 2 years and 4.7% (95% CI 4.31-5.20) at 5 years. The 1-year side-to-side differences were 0.97 mm (95% CI 0.90-1.03) in the ALD group and 1.45 mm (95% CI 1.41-1.49) in the FLD group. In the FLD group, 13% had a positive pivot shift, and in the ALD group, 6% had a positive pivot shift. There were no differences in KOOS. CONCLUSION: ALDs were non-inferior to FLDs regarding revision rates, knee stability, and patient-reported outcomes. Based on this conclusion, ALDs are safe to use for femoral fixation in ACLR. LEVEL OF EVIDENCE: III.

The Expert Next Door: Interactions With Friends and Family During the COVID-19 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic thrust the field of public health into the spotlight. For many epidemiologists, biostatisticians, and other public health professionals, this caused the professional aspects of our lives to collide with the personal, as friends and family reached out with concerns and questions. Learning how to navigate this space was new for many of us and required refining our communication style depending on context, setting, and audience. Some of us took to social media, utilizing our existing personal accounts to share information after sorting through and summarizing the rapidly emerging literature to keep loved ones safe. However, those in our lives sometimes asked unanswerable questions, or began distancing themselves when we suggested more stringent guidance than they had hoped for, causing additional stress during an already traumatic time. We often had to remind ourselves that we were also individuals experiencing this pandemic and that our time-intensive efforts were meaningful, relevant, and impactful. As this pandemic and other public health crises continue, we encourage members of our discipline to consider how we can best use shared lessons from this period and to recognize that our professional knowledge, when used in our personal lives, can promote, protect, and bolster confidence in public health.

Reinstatement of synaptic plasticity in the aging brain through specific dopamine transporter inhibition.

Aging-related neurological deficits negatively impact mental health, productivity, and social interactions leading to a pronounced socioeconomic burden. Since declining brain dopamine signaling during aging is associated with the onset of neurological impairments, we produced a selective dopamine transporter (DAT) inhibitor to restore endogenous dopamine levels and improve cognitive function. We describe the synthesis and pharmacological profile of (S,S)-CE-158, a highly specific DAT inhibitor, which increases dopamine levels in brain regions associated with cognition. We find both a potentiation of neurotransmission and coincident restoration of dendritic spines in the dorsal hippocampus, indicative of reinstatement of dopamine-induced synaptic plasticity in aging rodents. Treatment with (S,S)-CE-158 significantly improved behavioral flexibility in scopolamine-compromised animals and increased the number of spontaneously active prefrontal cortical neurons, both in young and aging rodents. In addition, (S,S)-CE-158 restored learning and memory recall in aging rats comparable to their young performance in a hippocampus-dependent hole board test. In sum, we present a well-tolerated, highly selective DAT inhibitor that normalizes the age-related decline in cognitive function at a synaptic level through increased dopamine signaling.

One-year outcome of brain injured patients undergoing early neurological rehabilitation: a prospective observational study.

BACKGROUND: The present study intended to analyze the outcome of patients with severe brain injury one-year after discharge from early rehabilitation. METHODS: Early neurological rehabilitation patients admitted to intensive or intermediate care units and discharged between June 2018 and May 2020 were screened for eligibility. The level of consciousness was evaluated using the Coma Recovery Scale-Revised (CRS-R) upon admission and at discharge. At one-year follow-up, the outcome was assessed with the Glasgow Outcome Scale-extended (GOSE). Demographical and clinical data collected during inpatient rehabilitation were used to predict the outcome 1 year after discharge. RESULTS: Two hundred sixty-four patients (174 males, 90 females) with a median age of 62 years (IQR = 51-75) and a median duration of their disease of 18 days (IQR = 12-28) were included in the study. At follow-up, the mortality rate was 27% (n = 71). Age and discharge CRS-R total score were independent predictors in a Cox proportional hazards model with death (yes/no) as the dependent variable. According to the GOSE interviews, most patients were either dead (n = 71; 27%), in a vegetative state (n = 28; 11%) or had a severe disability (n = 124; 47%), whereas only a few patients showed a moderate disability (n = 18; 7%) or a good recovery (n = 23; 9%) 1 year after discharge. Age, non-traumatic etiology, discharge CRS-R total score and length of stay independently predicted whether the outcome was good or poor at follow-up. CONCLUSION: Age was an important predictor for outcome at one-year follow-up, which might be due to altered brain plasticity and more comorbidities in elderly subjects. In addition, the present study demonstrated that the CRS-R total score at discharge might be more important for the prediction of one-year outcome than the initial assessment upon admission.

Validity of the Early Functional Ability scale (EFA) among critically ill patients undergoing early neurological rehabilitation.

BACKGROUND: A reliable assessment of the functional abilities of patients after severe brain damage is crucial for valid prognostication and treatment decisions, but most clinical scales are of limited use among this specific group of patients. AIM: The present study investigates the usefulness of the Early Functional Ability (EFA) scale, which determines the functional abilities of severely impaired patients. METHODS: Critically ill patients consecutively admitted to early neurological rehabilitation were screened for eligibility. We assessed the correlation between the EFA scale and (i) the Early Rehabilitation Barthel Index (ERBI), and (ii) the Coma Recovery Scale-Revised (CRS-R). The 1-year outcome on the Glasgow Outcome Scale-extended (GOSE) was used to examine the predictive validity. Demographical and medical variables were entered into univariate and multivariate binary regression models to identify independent predictors of 1-year outcome. RESULTS: Two hundred fifty-seven patients (168 men) with a median age of 62 years (IQR = 51-75) were enrolled. The correlation of the EFA scale with the CRS-R was high but low with the ERBI upon admission. Multivariate regression analysis yielded the vegetative subscale of the EFA scale as the only independent predictor for the 1-year outcome of patients admitted to early neurological rehabilitation. CONCLUSIONS: This study shows a high correlation of the EFA scale with the CRS-R but a weak correlation with the ERBI in patients with low functional abilities. With improving patient abilities, these correlations were partly reversed. Thus, the EFA scale is a useful tool to assess the functional abilities and the prognosis of critically ill patients adequately and may be more feasible than other scales.

Evaluation of the predictive validity of the Hessisch Oldendorf Risk of Falling Scale (HOSS).

OBJECTIVE: This study aims to further validate the Hessisch Oldendorf Risk of Falling Scale (HOSS) for neurological rehabilitation patients. DESIGN: The overall scale performance and fall rate was calculated in a retrospective data analysis. SETTING: The study was performed in a subacute care facility during inpatient neurological rehabilitation. SUBJECTS: The study population (n = 512) included neurological and neurosurgical patients with heterogeneous levels of disability. MAIN MEASURES: The HOSS total score and the suspected risk of falling were compared with the number of falls. Characteristics of fallers and non-fallers were compared using non-parametric group comparisons. Overall scale performance was assessed by calculating the area under the receiver operating characteristic curve of the HOSS as well as by calculating the sensitivity and specificity. RESULTS: A total of 82 (16%) patients experienced at least one fall. Fallers were characterized by an older age, a longer length of stay, a more severe impairment in the activities of daily living upon admission, a hemiparesis, an orientation disorder, a need of a walking aid device and an urinary incontinence. The number of falls was associated with the HOSS total score. Sixty-four fallers and two hundred seventy-four non-fallers were correctly categorized leading to a sensitivity of 78.0% and a specificity of 63.7%. The area under the receiver operating characteristic curve of the HOSS was 0.778 ± 0.25 (CI = 0.729-0.828, P < 0.001). CONCLUSION: The scale performance of the HOSS showed a good sensitivity and an adequate specificity to identify neurological patients who are at high risk of falling during inpatient rehabilitation.

Identification of Leishmania infantum and Leishmania braziliensis in captive primates from a zoo in Brazil.

Wild nonhuman primates (NHP) are considered natural hosts of a protozoan parasite from the genus Leishmania, the etiological agent of leishmaniasis. It is important to study the population of this infectious agent in zoo animals to establish surveillance and control mechanisms in Sorocaba through the application of a One Health approach, this is where human-animal-environment health and disease interface and can aid in the protection of endangered species. This study aimed to identify Leishmania infantum and Leishmania braziliensis in NHP living in a city where leishmaniasis is endemic. DNA was extracted from 48 NHP and analyzed using polymerase chain reaction primers that are specific for the species L. infantum and L. braziliensis. The results of our research revealed the first report of L. infantum and L. braziliensis naturally infecting primates at Sorocaba zoo. One primate from the species Plecturocebus vieirai was positive for L. infantum and five primates (four Alouatta caraya and one Ateles chamek) were positive for L. braziliensis. This indicates a possible role of these animals on the maintenance of these parasites.

Enriched Environment Attenuates Enhanced Trait Anxiety in Association with Normalization of Aberrant Neuro-Inflammatory Events.

Neuroinflammation is discussed to play a role in specific subgroups of different psychiatric disorders, including anxiety disorders. We have previously shown that a mouse model of trait anxiety (HAB) displays enhanced microglial density and phagocytic activity in key regions of anxiety circuits compared to normal-anxiety controls (NAB). Using minocycline, we provided causal evidence that reducing microglial activation within the dentate gyrus (DG) attenuated enhanced anxiety in HABs. Besides pharmacological intervention, "positive environmental stimuli", which have the advantage of exerting no side-effects, have been shown to modulate inflammation-related markers in human beings. Therefore, we now investigated whether environmental enrichment (EE) would be sufficient to modulate upregulated neuroinflammation in high-anxiety HABs. We show for the first time that EE can indeed attenuate enhanced trait anxiety, even when presented as late as adulthood. We further found that EE-induced anxiolysis was associated with the attenuation of enhanced microglial density (using Iba-1 as the marker) in the DG and medial prefrontal cortex. Additionally, EE reduced Iba1 + CD68+ microglia density within the anterior DG. Hence, the successful attenuation of trait anxiety by EE was associated in part with the normalization of neuro-inflammatory imbalances. These results suggest that pharmacological and/or positive behavioral therapies triggering microglia-targeted anti-inflammatory effects could be promising as novel alternatives or complimentary anxiolytic therapeutic approaches in specific subgroups of individuals predisposed to trait anxiety.

Evaluation of commercially available immuno-magnetic agglutination in comparison to enzyme-linked immunosorbent assays for rapid point-of-care diagnostics of COVID-19.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is caused by Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Fast, accurate, and simple blood-based assays for quantification of anti-SARS-CoV-2 antibodies are urgently needed to identify infected individuals and keep track of the spread of disease. METHODS: The study included 33 plasma samples from 20 individuals with confirmed COVID-19 by real-time reverse-transcriptase polymerase chain reaction and 40 non-COVID-19 plasma samples. Anti-SARS-CoV-2 immunoglobulin M (IgM)/immunoglobulin A (IgA) or immunoglobulin G (IgG) antibodies were detected by a microfluidic quantitative immunomagnetic assay (IMA) (ViroTrack Sero COVID IgM + IgA/IgG Ab, Blusense Diagnostics) and compared to an enzyme-linked immunosorbent assay (ELISA) (EuroImmun Medizinische Labordiagnostika). RESULTS: Of the 33 plasma samples from the COVID-19 patients, 28 were positive for IgA/IgM or IgG by IMA and 29 samples were positive by ELISA. Sensitivity for only one sample per patient was 68% for IgA + IgM and 75% IgG by IMA and 80% by ELISA. For samples collected 14 days after symptom onset, the sensitivity of both IMA and ELISA was around 91%. The specificity of the IMA reached 100% compared to 95% for ELISA IgA and 97.5% for ELISA IgG. CONCLUSION: IMA for COVID-19 is a rapid simple-to-use point-of-care test with sensitivity and specificity similar to a commercial ELISA.

Mitochondrial and Clearance Impairment in p.D620N VPS35 Patient-Derived Neurons.

BACKGROUND: VPS35 is part of the retromer complex and is responsible for the trafficking and recycling of proteins implicated in autophagy and lysosomal degradation, but also takes part in the degradation of mitochondrial proteins via mitochondria-derived vesicles. The p.D620N mutation of VPS35 causes an autosomal-dominant form of Parkinson's disease (PD), clinically representing typical PD. OBJECTIVE: Most of the studies on p.D620N VPS35 were performed on human tumor cell lines, rodent models overexpressing mutant VPS35, or in patient-derived fibroblasts. Here, based on identified target proteins, we investigated the implication of mutant VPS35 in autophagy, lysosomal degradation, and mitochondrial function in induced pluripotent stem cell-derived neurons from a patient harboring the p.D620N mutation. METHODS: We reprogrammed fibroblasts from a PD patient carrying the p.D620N mutation in the VPS35 gene and from two healthy donors in induced pluripotent stem cells. These were subsequently differentiated into neuronal precursor cells to finally generate midbrain dopaminergic neurons. RESULTS: We observed a decreased autophagic flux and lysosomal mass associated with an accumulation of α-synuclein in patient-derived neurons compared to controls. Moreover, patient-derived neurons presented a mitochondrial dysfunction with decreased membrane potential, impaired mitochondrial respiration, and increased production of reactive oxygen species associated with a defect in mitochondrial quality control via mitophagy. CONCLUSION: We describe for the first time the impact of the p.D620N VPS35 mutation on autophago-lysosome pathway and mitochondrial function in stem cell-derived neurons from an affected p.D620N carrier and define neuronal phenotypes for future pharmacological interventions. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.