In vitro evaluation of using ceftazidime/avibactam against carbapenem-resistant Acinetobacter baumannii.

OBJECTIVE: Carbapenem-resistant Acinetobacter baumannii (CRAB) is a global concern as effective treatments are very limited. We previously used a modified susceptibility testing approach to predict growth suppression in carbapenem-resistant Enterobacterales, but there are uncertainties about the generalizability of the model. The objective of this study is to verify if a similar approach can be extended to CRAB. METHOD: A clinical isolate of CRAB resistant to ceftazidime/avibactam (CAZ/AVI, MIC=32/4 mg/L) was examined. CAZ susceptibility was determined using increasing concentrations of AVI (0-64 mg/L), and MIC reduction was characterized with a sigmoid inhibitory maximum effect (Emax) model. The effectiveness of CAZ/AVI was validated in a hollow fiber infection model (HFIM) over 72 hours, using simulated unbound serum / epithelial lining fluid (ELF) exposures of 2.5 g over 2 hours every 8 hours. Baseline inocula of approximately 5.5 log CFU/mL were examined. RESULTS: An AVI concentration-dependent reduction in CAZ MIC was observed (r2=0.99). Ceftazidime MIC was dramatically reduced from 512 mg/L (no AVI) to 32 mg/L (AVI=4 mg/L), and further to 8 mg/L (AVI=16 mg/L). Pharmacokinetic simulations were satisfactory in the HFIM (r2>0.96). Bacterial suppression was observed > 24 hours with the serum exposure, but not that from the ELF. CONCLUSION: Using multiple AVI concentrations within the clinically relevant range, our susceptibility testing approach could have better insights of treatment outcome for infections caused by CRAB. This could potentially lead to effective intervention(s) overlooked by conventional susceptibility testing method. This case highlights the importance of site-specific drug exposures on determining treatment outcome.

"You know that we travel a lot": Mobility narratives among female sex workers living with HIV in Tanzania and the Dominican Republic.

Female sex workers (FSW) are highly mobile, which may result in reduced access to and use of health services and increased risk for poor health outcomes, particularly for those living with HIV. Mobility includes spatial, temporal, and social elements that are not fully captured by quantitative measures. We conducted two rounds of in-depth interviews with FSW living with HIV in Iringa, Tanzania (n = 20), and Santo Domingo, Dominican Republic (n = 20), to describe mobility experiences and compare mobility narratives across settings. We integrated a thematic analysis of all interviews with a narrative analysis of a subset of 10 information-rich interviews (five in each country) with women who had recently traveled, for sex work or another reason, outside of their hometown. Across narratives, FSW living with HIV traveled locally or to seasonal destinations, for short and long periods. Social factors influencing mobility included economic drivers; risk of arrest, harassment, or violence; anonymity and/or familiarity; social relationships; and clients' mobility. Spatial, temporal, and social factors intersected in unique ways in FSW's mobility experiences, yet distinct mobility typologies were evident across settings and destinations. Together, mobility narratives of FSW living with HIV can inform quantitative research on mobility typologies in Tanzania, the Dominican Republic, and elsewhere. With the potential for economic circumstances, climate change, and other emergencies to increase people's mobility around the world, researchers and practitioners can learn from the lived experiences of FSW to inform whether and how to tailor and improve the accessibility of HIV care and treatment interventions based on spatial, temporal, and social characteristics of mobility.

Getting Precise about Gender and Sex Measurement: A Primer for Epidemiologists.

Accurately measuring gender and sex is crucial in public health and epidemiology. Iteratively reexamining how variables-including gender and sex-are conceptualized and operationalized is necessary to achieve impactful research. Reexamining gender and sex advances epidemiology toward its goals of health promotion and disease elimination. While we cannot reduce the complexities of sex and gender to simply an issue of measurement, striving to capture these concepts and experiences accurately must be an ongoing dialogue and practice-to the benefit of the field and population health. We assert that epidemiology must counteract misconceptions and accurately measure gender and sex in epidemiology. We aim to summarize existing critiques and guiding principles in measuring gender and sex that can be applied in practice.

Scanning the aged to minimize missed injury: An EAST multicenter study.

BACKGROUND: Despite the high incidence of blunt trauma in older adults, there is a lack of evidence-based guidance for computed tomography (CT) imaging in this population. We aimed to identify an algorithm to guide use of a Pan-Scan (Head/C-spine/Torso) or a Selective Scan (Head/C-spine ± Torso). We hypothesized that a patient's initial history and exam could be used to guide imaging. METHODS: We prospectively studied blunt trauma patients aged 65+ at 18 Level I/II trauma centers. Patients presenting >24 h after injury or who died upon arrival were excluded. We collected history and physical elements and final injury diagnoses. Injury diagnoses were categorized into CT body regions of Head/C-spine or Torso (chest, abdomen/pelvis, and T/L spine). Using machine learning and regression modeling as well as a priori clinical algorithms based, we tested various decision rules against our dataset. Our priority was to identify a simple rule which could be applied at the bedside, maximizing sensitivity (Sens) and negative predictive value (NPV) to minimize missed injuries. RESULTS: We enrolled 5,498 patients with 3,082 injuries. Nearly half (47.1%, n = 2,587) had an injury within the defined CT body regions. No rule to guide a Pan-Scan could be identified with suitable Sens/NPV for clinical use. A clinical algorithm to identify patients for Pan-Scan, using a combination of physical exam findings and specific high-risk criteria, was identified and had a Sens of 0.94 and NPV of 0.86 This rule would have identified injuries in all but 90 patients (1.6%) and would theoretically spare 11.9% (655) of blunt trauma patients a torso CT. CONCLUSIONS: Our findings advocate for Head/Cspine CT in all geriatric patients with the addition of torso CT in the setting of positive clinical findings and high-risk criteria. Prospective validation of this rule could lead to streamlined diagnostic care of this growing trauma population. LEVEL OF EVIDENCE: Level 2, Diagnostic Tests or Criteria.

Mechanisms of gelofusine protection in an in vitro model of polymyxin B-associated renal injury.

Polymyxins are a last-resort treatment option for multidrug-resistant gram-negative bacterial infections, but they are associated with nephrotoxicity. Gelofusine was previously shown to reduce polymyxin-associated kidney injury in an animal model. However, the mechanism(s) of renal protection has not been fully elucidated. Here, we report the use of a cell culture model to provide insights into the mechanisms of renal protection. Murine epithelial proximal tubular cells were exposed to polymyxin B. Cell viability, lactate dehydrogenase (LDH) release, polymyxin B uptake, mitochondrial superoxide production, nuclear morphology, and apoptosis activation were evaluated with or without concomitant gelofusine. A megalin knockout cell line was used as an uptake inhibition control. Methionine was included in selected experiments as an antioxidant control. A polymyxin B concentration-dependent reduction in cell viability was observed. Increased viability was observed in megalin knockout cells following comparable polymyxin B exposures. Compared with polymyxin B exposure alone, concomitant gelofusine significantly increased cell viability as well as reduced LDH release, polymyxin B uptake, mitochondrial superoxide, and apoptosis. Gelofusine and methionine were more effective at reducing renal cell injury in combination than either agent alone. In conclusion, the mechanisms of renal protection by gelofusine involve decreasing cellular drug uptake, reducing subsequent oxidative stress and apoptosis activation. These findings would be valuable for translational research into clinical strategies to attenuate drug-associated acute kidney injury.NEW & NOTEWORTHY Gelofusine is a gelatinous saline solution with the potential to attenuate polymyxin-associated nephrotoxicity. We demonstrated that the mechanisms of gelofusine renal protection involve reducing polymyxin B uptake by proximal tubule cells, limiting subsequent oxidative stress and apoptosis activation. In addition, gelofusine was more effective at reducing cellular injury than a known antioxidant control, methionine, and a megalin knockout cell line, indicating that gelofusine likely has additional pharmacological properties besides only megalin inhibition.

Determining the MMPI-3 SUI scale's cross-sectional and prospective utility in suicide risk assessment.

OBJECTIVE: In-depth suicide risk assessments are particularly important to long-term suicide prevention. Broadband measures of psychopathology, such as the Minnesota Multiphasic Personality Inventory (MMPI) instruments, assess suicide risk factors and various mental health comorbidities. With the recent release of the MMPI-3, the Suicidal/Death Ideation (SUI) scale underwent revisions to improve its construct validity and detection of suicide risk factors. Thus, we hypothesized the MMPI-3 SUI scale would demonstrate medium to large associations with suicidal experience and behaviors, future ideation, and interpersonal risk factors of suicide. METHODS: A sample of 124 college students screened for elevated depressive symptoms completed a brief longitudinal study. Participants completed a baseline session including the MMPI-3 and criterion measures and three brief follow-ups every 2 weeks. RESULTS: SUI scores were most robustly associated with increased risk for past suicidal ideation, planning, and perceived burdensomeness. Prospectively assessed suicidal ideation was also meaningfully associated with SUI. SUI scale elevations indicate an increased risk of suicide-related risk factors. CONCLUSION: The MMPI-3 is a valuable tool to inform long-term suicide prevention for those experiencing elevated depressive symptoms as the SUI scale can assess past, current, and future suicide-related risk factors, including suicidal ideation and behaviors.

When Minutes Matter: A Comparison of Whole Blood Collection Techniques.

BACKGROUND: Fast and reliable blood collection is critical to emergency walking blood banks (WBB) because mortality significantly declines when blood is quickly administered to a warfighter with hemorrhagic shock. Phlebotomy for WBB is accomplished via either the "straight stick" (SS) or "ruggedized lock" (RL) method. SS comprises a 16-gauge phlebotomy needle connected to a blood collection bag via tubing. The RL device collects blood through the same apparatus, but has a capped, intravenous (IV) catheter between the needle and the donor's arm. This is the first study to compare these two methods in battlefield-relevant metrics. METHODS: Military first responders and licensed medical providers (N=86) were trained in SS and RL as part of fresh whole blood training exercises. Outcomes included venipuncture success rates, time to IV access, blood collection times, total time, and user preferences, using a within-subjects crossover design. Data were analyzed using ANOVA and nonparametric statistics at p<0.05. RESULTS: SS outperformed RL in first venipuncture success rates (76% vs. 64%, p=0.07), IV access times (448 [standard error of the mean; SE 23] vs. 558 [SE 31] s, p<0.01), and blood collection bag fill times (573 [SE 48] vs. 703 [SE 44] s, p<0.05), resulting in an approximate 3.5-minute faster time overall. Survey data were mixed, with users perceiving SS as simpler and faster, but RL as more reliable and secure. CONCLUSION: SS is optimal when timely collection is imperative, while RL may be preferable when device stability or replacing the collection bag is a consideration.

Behavioral and transcriptomic analyses of mecp2 function in zebrafish.

Rett syndrome (RTT), a human neurodevelopmental disorder characterized by severe cognitive and motor impairments, is caused by dysfunction of the conserved transcriptional regulator Methyl-CpG-binding protein 2 (MECP2). Genetic analyses in mouse Mecp2 mutants, which exhibit key features of human RTT, have been essential for deciphering the mechanisms of MeCP2 function; nonetheless, our understanding of these complex mechanisms is incomplete. Zebrafish mecp2 mutants exhibit mild behavioral deficits but have not been analyzed in depth. Here, we combine transcriptomic and behavioral assays to assess baseline and stimulus-evoked motor responses and sensory filtering in zebrafish mecp2 mutants from 5 to 7 days post-fertilization (dpf). We show that zebrafish mecp2 function is required for normal thigmotaxis but is dispensable for gross movement, acoustic startle response, and sensory filtering (habituation and sensorimotor gating), and reveal a previously unknown role for mecp2 in behavioral responses to visual stimuli. RNA-seq analysis identified a large gene set that requires mecp2 function for correct transcription at 4 dpf, and pathway analysis revealed several pathways that require MeCP2 function in both zebrafish and mammals. These findings show that MeCP2's function as a transcriptional regulator is conserved across vertebrates and supports using zebrafish to complement mouse modeling in elucidating these conserved mechanisms.

Assessment of PTSD and Trauma Symptoms With the MMPI-3 in College Students: Validity and Incremental Utility of the Anxiety Related Experiences (ARX) Scale.

Post Traumatic Stress Disorder (PTSD) is heterogeneous in nature, which complicates diagnostic efforts and makes accurate assessment tools critical. The MMPI family of instruments are widely used broadband measures of psychopathology, including trauma symptomology. The MMPI-3's Anxiety Related Experiences scale (ARX) is an expansion of the MMPI-2-RF Anxiety (AXY) scale which has historically represented the MMPI family's best measure of trauma symptoms. This study expands research on ARX in 2 samples of college students (n = 332 [PCL-5 Criterion] & n = 58 [CAPS-5 Criterion]) by examining ARX's incremental, criterion, and classification validity. ARX incrementally predicted PCL-5 total and cluster scores beyond that accounted for by AXY (R2Δ = .01-.09). ARX accounted for the most unique variance, beyond RCd and RC7, in CAPS-5 interview ratings of intrusion symptoms (R2Δ = .16). ARX was strongly related to trauma symptomology broadly (r = .42-.58) and demonstrated strong screening ability at T65 (sensitivity = .37-.40; specificity = .91-.92) and stronger diagnostic screening at T75 (sensitivity = .31; specificity = .93). We discuss clinical considerations when using ARX for assessing PTSD.

Feasibility Cues during a Sexual Encounter Impact the Strength of Heterosexual Women's Orgasm Goal Pursuit.

The "orgasm gap" for women who have sex with men remains a pressing gender equity issue. Recent research found that women who pursued orgasm as a goal were more likely to have one. The current research replicated this relationship between orgasm goal pursuit and orgasm frequency for heterosexual women, and found that this relationship did not exist for heterosexual men (Study 1). Then, across two experimental studies, we examined how heterosexual women vary their orgasm goal pursuit across sexual encounters. In Study 2, women who read that a hypothetical sexual encounter would be "quick" reported less intent to pursue orgasm than women who were told they could "take their time" or received no time information. In Study 3, women who read that their hypothetical sexual partner seemed selfish reported less intent to pursue orgasm than women who were given a non-selfish partner or no partner information. Importantly, these effects were mediated by women's perceived orgasm likelihood in the scenario. These results suggest that women shift their pursuit of orgasm depending on cues which signal whether orgasm will be feasible. This research used self-regulation theory to understand women's motivations for pursuing orgasm during sexual encounters with men, with implications for reducing the orgasm gap.

Cross validation of the Personality Assessment Inventory (PAI) Cognitive Bias Scale of Scales (CB-SOS) over-reporting indicators in a military sample.

Following the development of the Cognitive Bias Scale (CBS), three other cognitive over-reporting indicators were created. This study cross-validates these new Cognitive Bias Scale of Scales (CB-SOS) measurements in a military sample and contrasts their performance to the CBS. We analyzed data from 288 active-duty soldiers who underwent neuropsychological evaluation. Groups were established based on performance validity testing (PVT) failure. Medium effects (d = .71 to .74) were observed between those passing and failing PVTs. The CB-SOS scales have high specificity (≥.90) but low sensitivity across the suggested cut scores. While all CB-SOS were able to achieve .90, lower scores were typically needed. CBS demonstrated incremental validity beyond CB-SOS-1 and CB-SOS-3; only CB-SOS-2 was incremental beyond CBS. In a military sample, the CB-SOS scales have more limited sensitivity than in its original validation, indicating an area of limited utility despite easier calculation. The CBS performs comparably, if not better, than CB-SOS scales. CB-SOS-2's differences in performance in this study and its initial validation suggest that its psychometric properties may be sample dependent. Given their ease of calculation and relatively high specificity, our study supports the interpretation of elevated CB-SOS scores indicating those who are likely to fail concurrent PVTs.

Investigating the Validity of the MMPI-3 Eating Concerns (EAT) scale across Men and Women in a University Sample.

Disordered eating is a major health epidemic that occurs at disproportionate rates among young adults and for which gender plays a major role in symptom presentation. Broadband psychological instruments have historically not included disordered eating as a core scale construct. The recent release of the Minnesota Multiphasic Personality Inventory-3 (MMPI-3) offers an opportunity to address this shortcoming through the newly developed Eating Concerns Scale (EAT) for which the existing literature is promising but limited. This study expands research on EAT by investigating its validity and comparing findings across gender. In 345 college students (102 men, 243 women), we examined gender differences between men and women in the EAT scale's structure, item endorsement rates, mean scores, and correlations with measures of body image and eating pathology. Differences emerged in item endorsement rate, scale score elevation rate, and correlation magnitudes. Broadly, findings further support EAT's use in detecting eating pathology and highlight ways in which the EAT scale may not effectively capture masculine expressions of eating pathology, namely binging and purging behaviors. To assess eating pathology more comprehensively, clinicians and researchers should consider including assessments of eating pathology inclusive of masculine eating patterns. Limitations and future research directions are also discussed.

Systemic Arterial Oxygen Levels Differentiate Pre- and Post-capillary Predominant Hemodynamic Abnormalities During Exercise in Undifferentiated Dyspnea on Exertion.

BACKGROUND: Whether systemic oxygen levels (SaO2) during exercise can provide a window into invasively derived exercise hemodynamic profiles in patients with undifferentiated dyspnea on exertion is unknown. METHODS: We performed cardiopulmonary exercise testing with invasive hemodynamic monitoring and arterial blood gas sampling in individuals referred for dyspnea on exertion. Receiver operator analysis was performed to distinguish heart failure with preserved ejection fraction from pulmonary arterial hypertension. RESULTS: Among 253 patients (mean ± SD, age 63 ± 14 years, 55% female, arterial O2 [PaO2] 87 ± 14 mmHg, SaO2 96% ± 4%, resting pulmonary capillary wedge pressure [PCWP] 18 ± 4mmHg, and pulmonary vascular resistance [PVR] 2.7 ± 1.2 Wood units), there was no exercise PCWP threshold, measured up to 49 mmHg, above which hypoxemia was consistently observed. Exercise PaO2 was not correlated with exercise PCWP (rho = 0.04; P = 0.51) but did relate to exercise PVR (rho = -0.46; P < 0.001). Exercise PaO2 and SaO2 levels distinguished left-heart-predominant dysfunction from pulmonary-vascular-predominant dysfunction with an area under the curve of 0.89 and 0.89, respectively. CONCLUSION: Systemic O2 levels during exercise distinguish relative pre- and post-capillary pulmonary hemodynamic abnormalities in patients with undifferentiated dyspnea. Hypoxemia during upright exercise should not be attributed to isolated elevation in left heart filling pressures and should prompt consideration of pulmonary vascular dysfunction.

Improving maternal update rates within the first hour of NICU admission.

BACKGROUND: Timely communication is essential in attaining maternal satisfaction, developing an excellent physician-patient rapport, and increasing trust. This study reports a significant improvement in maternal communication rates through the quality improvement method. METHODS: An educational module was developed, and NICU staff was presented with the slides, followed by a performance questionnaire to demonstrate understanding. The first phase was completed by obtaining feedback from mothers through a questionnaire. The first plan-do-study-act (PDSA) cycle, carried out for eight weeks looking at the rates of the maternal update provided within an hour of admission of their neonates to the NICU, was followed by the second PDSA cycle, carried out for ten weeks. The improvement was calculated using conventional statistics and a statistical process control chart. RESULTS: During the first phase of the study, thirty-six percent of the mothers were updated within an hour of admission of their neonates to the NICU. During the first PDSA cycle, we did not notice a special cause variation or process change. A significant shift, eight consecutive points above the mean, was noted on the control chart during PDSA cycle 2. The mean±SD of the weekly update rate increased significantly during PDSA cycle 2 (76.8±11) compared to PDSA cycle 1 (47.5±14), p-value = 0.0002. CONCLUSION: We improved the maternal update rates through the educational module following the QI improvement model using the PDSA cycles.

Evaluation of a Passive Wearable Device for Post-Stroke Shoulder Abduction Support.

Post-stroke upper extremity function can be improved by devices that support shoulder abduction. However, many of these devices provide limited assistance in activities of daily living due to their complexity and encumbrance. We developed and evaluated a passive, lightweight (0.6 kg) wearable device consisting of an aluminum frame and elastic bands attached to a posture vest to aid in shoulder abduction. The number and thickness of bands can be adjusted to provide supportive forces to the affected arm. We measured reachable workspace area and Wolf Motor Function Test (WMFT) performance in people with a history of stroke (n = 11) with and without the wearable. The device increased workspace area in 6 participants and improved average WMFT functional and timing scores in 7 and 12 tasks, respectively, out of 16 total tasks. On average, participants increased their arm motion within 20 cm of shoulder level by 22.4% and decreased their hand's average distance from trunk by 15.2%, both improvements in the device case.

Accuracy of portable ultrasound for obstetric biometry.

OBJECTIVE: We assessed the accuracy of two portable ultrasound machines (PUM) in obtaining fetal biometry and estimating gestational age. METHODS: We analyzed data from the Fetal Age Machine Learning Initiative, an observational study of pregnant women in the United States and Zambia. Each participant underwent assessment by an experienced sonographer using both a high-specification ultrasound machine (HSUM) and a PUM (either Butterfly iQ or Clarius C3) to measure fetal biometry and calculate estimated gestational age (EGA) at each visit. Through comparison of paired PUM-HSUM scans, we estimated agreement between individual biometry measurements and aggregate gestational age estimates by reporting mean difference, along with intraclass correlation coefficient (ICC) and Bland-Altman plots, adjusting for trend. RESULTS: 881 participants contributed 1386 paired PUM-HSUM ultrasound studies between April and December 2021. PUM studies included 991 Butterfly and 395 Clarius. Gestational age at scan ranged from 7 to 38 weeks. Compared to HSUM, the Butterfly PUM had a mean difference of -0.20 days (95%CI±0.40) in the 1st trimester and -0.68 days (95%CI±0.68) in the 2nd/3rd trimesters. Also compared to HSUM, the Clarius PUM had a mean difference of 0.47 days (95%CI±0.64) in the 1st trimester and -1.67 days (95%CI±0.43) in the 2nd/3rd trimesters. ICCs were 0.989 or greater throughout. Increasing gestational age was associated with increasing error and absolute error. Both PUM devices demonstrated a modest trend toward underestimation of EGA at advancing gestational ages in 2nd/3rd trimester scans, compared to HSUM. CONCLUSION: Both the Butterfly iQ and Clarius C3 PUM devices were highly accurate in performing fetal biometry in a diverse population from the US and Zambia. This article is protected by copyright. All rights reserved.

MiR-324-5p inhibition after intrahippocampal kainic acid-induced status epilepticus does not prevent epileptogenesis in mice.

Background: Acquired epilepsies are caused by an initial brain insult that is followed by epileptogenesis and finally the development of spontaneous recurrent seizures. The mechanisms underlying epileptogenesis are not fully understood. MicroRNAs regulate mRNA translation and stability and are frequently implicated in epilepsy. For example, antagonism of a specific microRNA, miR-324-5p, before brain insult and in a model of chronic epilepsy decreases seizure susceptibility and frequency, respectively. Here, we tested whether antagonism of miR-324-5p during epileptogenesis inhibits the development of epilepsy. Methods: We used the intrahippocampal kainic acid (IHpKa) model to initiate epileptogenesis in male wild type C57BL/6 J mice aged 6-8 weeks. Twenty-four hours after IHpKa, we administered a miR-324-5p or scrambled control antagomir intracerebroventricularly and implanted cortical surface electrodes for EEG monitoring. EEG data was collected for 28 days and analyzed for seizure frequency and duration, interictal spike activity, and EEG power. Brains were collected for histological analysis. Results: Histological analysis of brain tissue showed that IHpKa caused characteristic hippocampal damage in most mice regardless of treatment. Antagomir treatment did not affect latency to, frequency, or duration of spontaneous recurrent seizures or interictal spike activity but did alter the temporal development of frequency band-specific EEG power. Conclusion: These results suggest that miR-324-5p inhibition during epileptogenesis induced by status epilepticus does not convey anti-epileptogenic effects despite having subtle effects on EEG frequency bands. Our results highlight the importance of timing of intervention across epilepsy development and suggest that miR-324-5p may act primarily as a proconvulsant rather than a pro-epileptogenic regulator.

Contrasting MMPI-3 validity scale effectiveness differences across in-person and telehealth administration procedures.

Psychological assessment underwent substantive challenges and changes when the COVID-19 pandemic began, and these changes are likely to endure given the rapid growth of telehealth clinical practice and assessment research using virtual procedures. COVID-19-related changes to assessment practices have impacted accordingly how we study overreporting scale functioning, including the modality through which we administer measures. No available research provides direct comparisons of overreporting scale effectiveness within simulation research across in-person and telehealth modalities, despite early support for novel instruments relying on remote procedures within the historic context of the pandemic. We used simulated feigning conditions collected using best telehealth practices to examine if, and how, overreporting scales differed in effectiveness by evaluating mean scores, elevation rates, and classification accuracy statistics, relative to parallel in-person conditions. Results indicate no meaningful differences in scale effectiveness, particularly when exclusion procedures included a posttest questionnaire. Our findings support telehealth assessment practice and the integration of research collected virtually into the traditional, in-person feigning literature. Limitations and future directions are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Neurodevelopmental outcomes in children and adults with Fetal Valproate Spectrum Disorder: A contribution from the ConcePTION project.

AIM: To describe the neurodevelopmental phenotype of older children and adults with a diagnosis of Fetal Valproate Spectrum Disorder (FVSD). METHODS: In this cross-sectional study, 90 caregivers were recruited and completed a series of questionnaires regarding the neurodevelopmental outcomes of 146 individuals aged 7-37 years (M = 18.1), including individuals with a formal diagnosis of FVSD (n = 99), individuals exposed to Valproate but without an FVSD diagnosis (n = 24), and individuals not exposed to Valproate (N = 23). The mean dose of valproate exposure for individuals with an FVSD diagnosis was 1470 mg/day. RESULTS: Individuals with a diagnosis of FVSD showed significantly higher levels of moderate (43.4%) and severe (14.4%) cognitive impairment than other groups (p = 0.003), high levels of required formal educational support (77.6%), and poorer academic competence than individuals not exposed to Valproate (p = 0.001). Overall psychosocial problems (p = 0.02), internalising problems (p = 0.05) and attention problems (p = 0.001), but not externalising problems, were elevated in individuals with a diagnosis of FVSD. Rates of neurodevelopmental disorders, particularly autistic spectrum disorders (62.9%) and sensory problems (80.6%) are particularly central to the FVSD phenotype. There was no evidence of a statistical dose-dependent effect, possibly due to the high mean dose of exposure having a uniformly negative impact across the sample. Individuals with FVSD had required a significant number of health and child development services. INTERPRETATION: Children and young adults with a diagnosis of FVSD are at an increased risk of a range of altered neurodevelopmental outcomes, highlighting the need for a multidisciplinary approach to clinical management across the lifespan.

Zileuton ameliorates aminoglycoside and polymyxin-associated acute kidney injury in an animal model.

OBJECTIVES: Aminoglycosides and polymyxins are antibiotics with in vitro activity against MDR Gram-negative bacteria. However, their clinical use is hindered by dose-limiting nephrotoxicity. The objective of this project was to determine if zileuton can reduce nephrotoxicity associated with amikacin and polymyxin B in a rat model of acute kidney injury. METHODS: Sprague Dawley rats (n = 10, both genders) were administered either amikacin (300 mg/kg) or polymyxin B (20 mg/kg) daily for 10 days. Zileuton (4 and 10 mg/kg) was delivered intraperitoneally 15 min before antibiotic administration. Blood samples were collected at baseline and daily to determine serum creatinine concentration. Nephrotoxicity was defined as a ≥2× elevation of baseline serum creatinine. Time-to-event analysis and log rank test were used to compare the onset of nephrotoxicity in different cohorts. Histopathological analysis was also conducted to characterize the extent of kidney injury. RESULTS: Animals receiving amikacin or polymyxin B alone had nephrotoxicity rates of 90% and 100%, respectively. The overall rate was reduced to 30% in animals receiving adjuvant zileuton. The onset of nephrotoxicity associated with amikacin and polymyxin B was also significantly delayed by zileuton at 4 and 10 mg/kg, respectively. Histopathology confirmed reduced kidney injury in animals receiving amikacin concomitant with zileuton. CONCLUSIONS: Our pilot data suggest that zileuton has the potential to attenuate nephrotoxicity associated with last-line antibiotics. This would allow these antibiotics to treat MDR Gram-negative bacterial infections optimally without dose-limiting constraints. Further studies are warranted to optimize drug delivery and dosing in humans.