Leptospira infection in bats in Vietnam.

Bats from three provinces in Vietnam (Lai Chau, Son La, and Dong Thap) were examined for the presence of pathogenic Leptospira or specific antibodies using polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and microscopic agglutination test (MAT). Tissue specimens from 298 bats belonging to 11 species were analyzed using a real-time PCR assay specific for leptospires of pathogenic species. Leptospiral DNA was identified in 40 bats from following species: Rousettus amplexicaudatus (5/9; 55.5%), Rousettus leschenaultii (17/42; 40.4%), Myotis hasseltii (8/25; 32%), Taphozous longimanus (3/12; 25%), and Eonycteris spelaea (7/32; 21.9%). Based on secY phylogeny, sequences from M. hasseltii bore a strong resemblance to L. borgpetersenii. Sequences from other species revealed unique lineages: one of them resembled Leptospira sp., previously identified in Rousettus madagascariensis (Madagascar) and Rousettus aegyptiacus (South Africa); the second lineage showed close relation to L. kirshneri; and the third held an intermediary position between L. noguchii and L. interrogans. Through ELISA, anti-Leptospira antibodies were found in 83 of 306 bats, with the highest seroprevalence observed in R. leschenaultii (44/48; 91.6%), R. amplexicaudatus (6/8; 75%), and E. spelaea (19/25; 76%). 66 of these ELISA-positive samples were tested using MAT; 41 of them were confirmed in MAT as positive. The predominant serogroups in our study were Tarassovi and Mini.

Seraph 100 Microbind Affinity Blood Filter Does Not Clear Antibiotics: An Analysis of Antibiotic Concentration Data from PURIFY-OBS.

INTRODUCTION: Novel hemoperfusion systems are emerging for the treatment of sepsis. These devices can directly remove pathogens, pathogen-associated molecular patterns, cytokines, and other inflammatory markers from circulation. However, significant safety concerns such as potential antibiotic clearance need to be addressed prior to these devices being used in large clinical studies. METHODS: Prospective, observational study of 34 participants undergoing treatment with the Seraph 100® Microbind Affinity Blood Filter (Seraph 100) device at 6 participating sites in the USA. Patients were included for analysis if they had a record of receiving an antibiotic concurrent with Seraph 100 treatment. Patients were excluded if there was missing information for blood flow rate. Blood samples were drawn pre- and post-filter at 1 h and 4 h after treatment initiation. These average pre- and post-filter time-concentration observations were then used to estimate antibiotic clearance in L/h (CLSeraph) due to the Seraph 100 device. RESULTS: Of the 34 participants in the study, 17 met inclusion and exclusion criteria for the antibiotic analysis. Data were obtained for 7 antibiotics (azithromycin, cefazolin, cefepime, ceftriaxone, linezolid, piperacillin, and vancomycin) and one beta-lactamase inhibitor. Mean CLSeraph for the antibiotics investigated ranged from -0.57 to 0.47 L/h. No antibiotic had a CLSeraph statistically significant from 0. DISCUSSION/CONCLUSION: The Seraph 100 did not significantly clear any measured antibiotic in clinical samples. These data give further evidence to suggest that these therapies may be safely administered to critically ill patients and will not impact concentrations of administered antibiotics.

Daily Naltrexone Use Does Not Adversely Affect Physical, Cognitive or Marksmanship Performance in U.S. Army Soldiers.

INTRODUCTION: Considering the potential of weaponized opioids, evaluating how prophylactic countermeasures affect military-relevant performance is necessary. Naltrexone is a commercially available Food and Drug Administration-approved medication that blocks the effects of opioids with minimal side effects. However, the effects of naltrexone on the health and performance of non-substance abusing military personnel are not well described in the existing literature. METHODS: Active duty U.S. Army Soldiers (n = 16, mean ± SD, age: 23.1 ± 5.3 y) completed a series of physical, cognitive, and marksmanship tasks during a 4-day pretrial, a 7-day active trial, and a 4-day post-trial phase. During the active trial, participants were administered 50 mg of oral naltrexone daily. Physiological and biological processes were monitored with a daily review of systems, sleep monitoring, biochemistry, and hematology blood panels. RESULTS: Naltrexone did not negatively affect physical performance, cognitive functioning, marksmanship, or sleep duration (P > 0.05). Improvements were observed during the active trial compared to the pretrial phase in cognitive tasks measuring logical relations (P = 0.05), matching to sample (P = 0.04), math speed (P < 0.01), math percent correct (P = 0.04), and spatial processing (P < 0.01). Results from biochemistry and hematology blood panels remained within clinically normative ranges throughout all phases of the study. No participants were medically withdrawn; however, one participant voluntarily withdrew due to nausea and reduced appetite. CONCLUSIONS: Temporary (7-day) daily use of naltrexone was safe and did not negatively affect physical performance, cognitive functioning, marksmanship ability, or sleep in a healthy cohort of U.S. Army Soldiers.

Plasma Blood Levels of Tafenoquine following a Single Oral Dosage in BALBc Mice with Acute Babesia microti Infection That Resulted in Rapid Clearance of Microscopically Detectable Parasitemia.

Previous studies of mice infected with Babesia microti have shown that a single dose of tafenoquine administered orally is extremely effective at decreasing microscopically detectable parasitemia. However, a critical limitation of studies to date is the lack of data concerning the plasma levels of tafenoquine that are needed to treat babesiosis. In the current study, we begin to address this gap by examining the plasma levels of tafenoquine associated with the rapid reduction of B. microti patent parasitemia in a mouse model of babesiosis. In the current study, we infected BALB/c mice with 1 × 107B. microti-infected red blood cells. Two days post-infection, mice were treated with 20 mg/kg of tafenoquine succinate or vehicle control administered orally by gavage. Parasitemia and plasma levels of tafenoquine were evaluated every 24 h post-treatment for 96 h. This allowed us to correlate blood plasma levels of tafenoquine with reductions in parasitemia in treated mice. Consistent with previous studies, a single oral dose of 20 mg/kg tafenoquine resulted in a rapid reduction in parasitemia. Plasma levels of tafenoquine 24 h post-administration ranged from 347 to 503 ng/mL and declined thereafter. This blood plasma tafenoquine level is similar to that achieved in humans using the current FDA-approved dose for the prevention of malaria.

Detection of Filoviruses in Bats in Vietnam.

A new filovirus named Menglà virus was found in bats in southern China in 2015. This species has been assigned to the new genus Dianlovirus and has only been detected in China. In this article, we report the detection of filoviruses in bats captured in Vietnam. We studied 248 bats of 15 species caught in the provinces of Lai Chau and Son La in northern Vietnam and in the province of Dong Thap in the southern part of the country. Filovirus RNA was found in four Rousettus leschenaultii and one Rousettus amplexicaudatus from Lai Chau Province. Phylogenetic analysis of the polymerase gene fragment showed that three positive samples belong to Dianlovirus, and two samples form a separate clade closer to Orthomarburgvirus. An enzyme-linked immunosorbent assay showed that 9% of Rousettus, 13% of Eonycteris, and 10% of Cynopterus bats had antibodies to the glycoprotein of marburgviruses.

Response and recovery of endocrine, behavioral, and neuronal morphology outcomes after different traumatic stressor exposures in male rats.

Preclinical models of organismal response to traumatic stress (threat of death or serious injury) can be monitored using neuroendocrine, behavioral, and structural metrics. While many rodent models of traumatic stress have provided a glimpse into select components of the physiological response to acute and chronic stressors, few studies have directly examined the potential differences between stressors and their potential outcomes. To address this gap, we conducted a multi-level comparison of the immediate and longer-term effects of two types of acute traumatic stressors. Adult male rats were exposed to either underwater trauma (UWT), predator exposure (PE), or control procedural handling conditions. Over the next 7 days, yoked cohorts underwent either serial blood sampling for neuroendocrine evaluation across the circadian cycle, or repeated behavioral testing in the elevated plus maze. In addition, a subset of brains from the latter cohort were assessed for dendritic spine changes in the prefrontal cortex and basolateral amygdala. We observed stressor-dependent patterns of response and recovery across all measures, with divergence between endocrine responses despite similar behavioral outcomes. These results demonstrate that different stressors elicit unique behavioral, neuroendocrine, and neuro-structural response profiles and suggest that specific stress models can be used to model desired responses for specific preclinical applications, such as evaluations of underlying mechanisms or therapeutic candidates.

Potential role of fibroblast growth factor 21 in the deterioration of bone quality in impaired glucose tolerance.

PURPOSE: Findings on trabecular bone score (TBS), an index of bone quality, have been reported in prediabetes defined by impaired fasting glucose or HbA1c. Here, we assessed the bone mineral density (BMD) and TBS in prediabetes individuals with impaired glucose tolerance (IGT), and investigated the association of these bone parameters with serum levels of fibroblast growth factor 21 (FGF21), a hormone implicated in bone metabolism and with higher levels in IGT. METHODS: Chinese postmenopausal women aged 55-80 years, without diabetes, were recruited from the Hong Kong Cardiovascular Risk Factor Prevalence Study in 2016-2018. Normal glucose tolerance (NGT) was defined by fasting glucose < 5.6 mmol/L and 2-h plasma glucose (2hG) < 7.8 mmol/L, and IGT by 2hG 7.8-11 mmol/L. Serum levels of FGF21 and other bone metabolism regulators were measured. Insulin sensitivity was assessed by the Matsuda index. Independent determinants of TBS were evaluated using multivariable stepwise linear regression. RESULTS: 173 individuals with NGT and 73 with IGT were included. TBS was lower in those with IGT compared to those with NGT, while BMD was comparable. Individuals with IGT had significantly higher serum FGF21 levels, which in turn showed an independent inverse relationship with TBS, attenuated after inclusion of the Matsuda index. Serum FGF21 levels, however, did not correlate with BMD. CONCLUSION: Among Chinese postmenopausal women, bone quality was worse in IGT, despite comparable bone density. FGF21 levels showed a significant independent inverse relationship with TBS, partly attributed to insulin resistance. Whether FGF21 contributes to the impaired bone quality in IGT remains speculative.

Suspected heparin-induced thrombocytopenia in a COVID-19 patient on extracorporeal membrane oxygenation support: a case report.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) support can be life-saving in critically ill COVID-19 patients. However, there are many complications associated with this procedure, including Heparin-induced thrombocytopenia (HIT.) Despite its rarity in ECMO cases, HIT can lead to devastating consequences and is difficult to manage. CASE PRESENTATION: In this report, we present a case of a COVID-19 patient on ECMO support who was diagnosed with HIT and required intensive treatment. Initially, HIT was only suspected due to newly-developed thrombocytopenia and oxygenator dysfunction, with thrombi observed later. Regarding his treatment, since there was no recommended replacement to heparin available to us at the time of diagnosis, we decided to use rivaroxaban temporarily. No adverse events were recorded during that period. The patient was able to make a full recovery. CONCLUSION: HIT may jeopardize patient's care during ECMO. As COVID-19 may bring about a surge in the number of patients requiring ECMO support, we need consented guidance to optimize treatment in this specific situation.

Overexpression of bla OXA-58 Gene Driven by ISAba3 Is Associated with Imipenem Resistance in a Clinical Acinetobacter baumannii Isolate from Vietnam.

The aim of this study was to investigate genetic structures and expression of bla OXA-58 gene in five Acinetobacter baumannii clinical isolates recovered from two hospitals in southern Vietnam during 2012-2014. A. baumannii isolates were identified by automated microbiology systems and confirmed by PCR. All isolates were characterized as multidrug resistant by antimicrobial testing using the disk diffusion method. Four imipenem susceptible and one nonsusceptible isolates (MIC > 32 µg·ml-1) were identified by E-test. PCR amplification of bla OXA-58 gene upstream and downstream sequences revealed the presence of ISAba3 at both locations in one multidrug-resistant isolate. Semiquantitation of bla OXA-51 and bla OXA-58 gene expression was performed by the 2-ΔΔCt method. The bla OXA-51 gene expression of five isolates showed little difference, but the isolate bearing ISAba3-bla OXA-58-ISAba3 exhibited significantly higher bla OXA-58 mRNA level. Higher ß-lactamases activity in periplasmic than cytoplasmic fraction was found in most isolates. The isolate overexpressing bla OXA-58 gene possessed very high periplasmic enzyme activity. In conclusion, the A. baumannii isolate bearing ISAba3-bla OXA-58 gene exhibited high resistance to imipenem, corresponding to an overexpression of bla OXA-58 gene and very high periplasmic ß-lactamase activity.

Long-term postnatal outcome of fetuses with prenatally suspected septo-optic dysplasia.

OBJECTIVES: Septo-optic dysplasia (SOD) is a clinical syndrome characterized by varying combinations of optic nerve hypoplasia, pituitary gland hypoplasia and abnormal cavum septi pellucidi. It is suspected on prenatal imaging when there is non-visualization or hypoplasia of the septal leaflets. Long-term postnatal outcomes of fetuses with prenatally suspected SOD have been documented poorly. The aims of this study were to describe the natural history of deficient septal leaflets, to quantify the incidence of postnatally confirmed SOD and to document the visual, endocrine and long-term neurodevelopmental outcomes of these infants. METHODS: This was an observational retrospective study of all fetuses with prenatal imaging showing isolated septal agenesis, assessed at a single tertiary center over an 11-year period. Pregnancy, delivery and neonatal outcomes and pre- and postnatal imaging findings were reviewed. Neonatal evaluations or fetal autopsy reports were assessed for confirmation of SOD. Ophthalmologic, endocrine, genetic and long-term developmental evaluations were assessed. Imaging findings and outcome were compared between infants with and those without postnatally confirmed SOD. RESULTS: Of 214 fetuses presenting with septal absence on prenatal ultrasound and magnetic resonance imaging (MRI), 18 (8.4%) were classified as having suspected isolated septal agenesis suspicious for SOD. Uniform prenatal MRI findings in cases with suspected SOD included remnants of the leaflets of the cavum septi pellucidi, fused forniceal columns, normal olfactory bulbs and tracts and a normal optic chiasm. Twelve fetuses were liveborn and five (27.8%) had postnatally confirmed SOD. Only two of these five fetuses had additional prenatal imaging features (pituitary cyst, microphthalmia and optic nerve hypoplasia) supporting a diagnosis of SOD. The other three confirmed SOD cases had no predictive prenatal or postnatal imaging findings that reliably differentiated them from cases without confirmed SOD. Visual and endocrine impairments were present in two (40%) and four (80%) cases with confirmed SOD, respectively. In those with visual and/or endocrine impairment, developmental delay (median age at follow-up, 2.5 (interquartile range, 2.5-7.0) years) was common (80%) and mostly severe. Neonates with isolated septal agenesis and a lack of visual or endocrine abnormalities to confirm SOD had normal development. CONCLUSIONS: Only a quarter of fetuses with isolated septal agenesis suggestive of SOD will have postnatal confirmation of the diagnosis. Clinical manifestations of SOD are variable, but neurodevelopmental delay may be more prevalent than thought formerly. © 2020 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Beyond the Chief Complaint: Our Patients' Worries.

Fourth-year medical students at the University of Colorado School of Medicine distributed cards to patients in the emergency department asking, "What Worries You Most?" The patients' responses provided insight about their most pressing concerns, often unrelated to their "chief complaints."

Polyoxygenated steroids from the gorgonian Menella woodin with capabilities to modulate ROS levels in macrophages at response to LPS.

Four new polyoxygenated sterol derivatives (1-4) along with the compounds (5-7) previously known from other biological sources were isolated from the gorgonian Menella woodin, collected from the Vietnamese waters. Structures of 1-4 were elucidated by the detailed NMR spectroscopic and mass-spectrometric analyses as well as comparison with those reported in literature data. Compounds 1, 4, and 6 decrease the production of reactive oxygen species (ROS) by the murine macrophages of RAW 264.7 line at induction by endotoxic lipopolysaccharide (LPS) from Escherichia coli.

Tract-Based Spatial Statistics in Preterm-Born Neonates Predicts Cognitive and Motor Outcomes at 18 Months.

BACKGROUND AND PURPOSE: Adverse neurodevelopmental outcome is common in children born preterm. Early sensitive predictors of neurodevelopmental outcome such as MR imaging are needed. Tract-based spatial statistics, a diffusion MR imaging analysis method, performed at term-equivalent age (40 weeks) is a promising predictor of neurodevelopmental outcomes in children born very preterm. We sought to determine the association of tract-based spatial statistics findings before term-equivalent age with neurodevelopmental outcome at 18-months corrected age. MATERIALS AND METHODS: Of 180 neonates (born at 24-32-weeks' gestation) enrolled, 153 had DTI acquired early at 32 weeks' postmenstrual age and 105 had DTI acquired later at 39.6 weeks' postmenstrual age. Voxelwise statistics were calculated by performing tract-based spatial statistics on DTI that was aligned to age-appropriate templates. At 18-month corrected age, 166 neonates underwent neurodevelopmental assessment by using the Bayley Scales of Infant Development, 3rd ed, and the Peabody Developmental Motor Scales, 2nd ed. RESULTS: Tract-based spatial statistics analysis applied to early-acquired scans (postmenstrual age of 30-33 weeks) indicated a limited significant positive association between motor skills and axial diffusivity and radial diffusivity values in the corpus callosum, internal and external/extreme capsules, and midbrain (P < .05, corrected). In contrast, for term scans (postmenstrual age of 37-41 weeks), tract-based spatial statistics analysis showed a significant relationship between both motor and cognitive scores with fractional anisotropy in the corpus callosum and corticospinal tracts (P < .05, corrected). Tract-based spatial statistics in a limited subset of neonates (n = 22) scanned at <30 weeks did not significantly predict neurodevelopmental outcomes. CONCLUSIONS: The strength of the association between fractional anisotropy values and neurodevelopmental outcome scores increased from early-to-late-acquired scans in preterm-born neonates, consistent with brain dysmaturation in this population.

The relationship between parental fatigue, parenting self-efficacy and behaviour: implications for supporting parents in the early parenting period.

BACKGROUND: Emerging evidence indicates that parental fatigue is associated with low warmth and increased hostility in parent-child interactions. One possible pathway by which fatigue may impact on parenting behaviour is via parental self-efficacy (PSE), whereby high fatigue may undermine PSE, which is often associated with suboptimal parenting behaviour. The current study sought to explore a model of the relationships between parental fatigue, parenting warmth and hostility, where PSE mediates these relationships and whether the nature of these relationships differ by social or family context. METHODS: The current sample was drawn from a larger Australian community sample survey on parent well-being and parenting. It consisted of 1143 parents (mothers, n = 1003; fathers, n = 140) of children aged 0-4 years. RESULTS: Path analysis revealed that the relationship between fatigue and parenting warmth and hostility was fully mediated by PSE. CONCLUSIONS: These results indicate that fatigue has the potential to negatively influence parenting behaviours that are important for their children's well-being and development, and that fatigue plays a mediating role in this relationship. Implications of the study for psycho-education and interventions targeting the management of parental fatigue are discussed.

Weight as predictors of clinical progression and treatment failure: results from the TREAT Asia Pediatric HIV Observational Database.

OBJECTIVE: To evaluate the value of time-updated weight and height in predicting clinical progression, and immunological and virological failure in children receiving combination antiretroviral therapy (cART). METHODS: We used Cox regression to analyze data of a cohort of Asian children. RESULTS: A total of 2608 children were included; median age at cART was 5.7 years. Time-updated weight for age z score < -3 was associated with mortality (P < 0.001) independent of CD4% and < -2 was associated with immunological failure (P ≤ 0.03) independent of age at cART. CONCLUSIONS: Weight monitoring provides useful data to inform clinical management of children on cART in resource-limited settings.

Isolation, structures, and biological activities of triterpenoids from a Penares sp. marine sponge.

Six new triterpenoids (1-6) and the previously known penasterone, acetylpenasterol, and ergosta-4,24(28)-dien-3-one were isolated from a Penares sp. sponge collected from Vietnamese waters. Structures of the obtained compounds were established by extensive 1D and 2D NMR spectroscopy and mass spectrometry. Configurations of the triterpene epoxy lactones (1-4) were determined on the basis of NOESY and CD data and calculation of spin coupling constants and confirmed by X-ray crystallographic analysis of compound 2. The isolated triterpenoid 6 was cytotoxic against human leukemia HL-60 cells (IC50 = 9.7 µM).

Prenatal and postnatal inflammation in relation to cortisol levels in preterm infants at 18 months corrected age.

OBJECTIVE: To examine whether early inflammation is related to cortisol levels at 18 months corrected age (CA) in children born very preterm. STUDY DESIGN: Infants born ≤ 32 weeks of gestational age were recruited in the neonatal intensive care unit (NICU), and placental histopathology, magnetic resonance imaging (MRI) and chart review were obtained. At 18 months CA, developmental assessment and collection of three salivary cortisol samples were carried out. Generalized least squares was used to analyze data from 85 infants providing 222 cortisol samples. RESULT: Infants exposed to chorioamnionitis with funisitis had a significantly different pattern of cortisol across the samples compared with infants with chorioamnionitis alone or no prenatal inflammation (F(4, 139)=7.3996, P<0.0001). Postnatal infections, necrotizing enterocolitis and chronic lung disease were not significantly associated with the cortisol pattern at 18 months CA. CONCLUSION: In children born very preterm, prenatal inflammatory stress may contribute to altered programming of the hypothalamic-pituitary-adrenal (HPA) axis.

Diarylheptanoids and flavonoids from viscum album inhibit LPS-stimulated production of pro-inflammatory cytokines in bone marrow-derived dendritic cells.

Three new diarylheptanoids, (3S,5R)-3-hydroxy-5-methoxy-1,7-bis(4-hydroxyphenyl)-6E-heptene (1), (3S,5S)-3-hydroxy-5-methoxy-1,7-bis(4-hydroxyphenyl)-6E-heptene (2), and (3S)-3-hydroxy-1,7-bis(4-hydroxyphenyl)-6E-hepten-5-one (3), four new flavonoid glycosides, 3,7,3'-tri-O-methylquercetin-4'-O-ß-d-apiofuranosyl-(1→2)-O-ß-d-glucopyranoside (4), 7,3'-di-O-methylquercetin-4'-O-ß-d-glucopyranosyl-3-O-[6‴-(3-hydroxy-3-methylglutaroyl)]-α-d-glucopyranoside (5), 7,3'-di-O-methylquercetin-4'-O-ß-d-glucopyranosyl-3-O-[(6'''''→5'''')-O-1'''''-(sinap-4-yl)-ß-d-glucopyranosyl-6‴-(3-hydroxy-3-methylglutaroyl)]-α-d-glucopyranoside (6), and (2S)-5-hydroxy-7,3'-dimethoxyflavanone-4'-O-ß-d-apiofuranosyl-(1→5)-O-ß-d-apiofuranosyl-(1→2)-O-ß-d-glucopyranoside (9), and 17 known compounds were isolated from the leaves and twigs of Viscum album. Compounds 1, 4, and 19 significantly inhibited LPS-stimulated production of TNF-α, IL-6, and IL-12p40 with IC50 values ranging from 0.09 ± 0.01 to 8.96 ± 0.45 µM. (+)-Medioresinol (13) showed inhibitory effects on LPS-stimulated production of IL-12p40 with an IC50 value of 2.00 ± 0.15 µM.