Antiseptic management of critical wounds: differential bacterial response upon exposure to antiseptics and first insights into antiseptic/phage interactions - experimental studies.

BACKGROUND: With the antibiotic crisis, the topical antibacterial control including chronic wounds gains increasing importance. However, little is known regarding tolerance development when bacteria face repetitive exposure to the identical antiseptics as commonly found in clinical practice. MATERIALS AND METHODS: We exposed clinical isolates foremost of chronic wounds in vitro to dilutions of two antisepctics used for wound therapy: polyhexanide or octenidine. Adaptive response was determined by growth/kill curves, minimal inhibitory concentration (MIC), and whole genome sequencing. Antiseptic/bacteriophage combinations were studied by liquid-infection assays and bacterial plating. RESULTS: Polyhexanide acted stronger against Escherichia coli and Proteus mirabilis while octenidine was more potent against Staphylococcus aureus. Otherwise, the antiseptic efficacy varied across isolates of Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. Upon repetitive exposure with constant antiseptic concentrations P. aeruginosa and P. mirabilis adaptation was evident by a reduced lag-phase and a two-fold increased MIC. Under increasing octenidine concentrations, P. aeruginosa adapted to an eightfold higher dosage with mutations in smvA, opgH and kinB affecting an efflux pump, alginate and biofilm formation, respectively. S. aureus adapted to a fourfold increase of polyhexanide with a mutation in the multiple peptide resistance factor MprF, also conferring cross-resistance to daptomycin. Antiseptic/bacteriophage combinations enhanced bacterial inhibition and delayed adaptation. CONCLUSION: Different bacterial species/strains respond unequally to low-level antiseptic concentrations. Bacterial adaptation potential at phenotypic and genotypic levels may indicate the necessity for a more nuanced selection of antiseptics. Bacteriophages represent a promising yet underexplored strategy for supporting antiseptic treatment which may be particularly beneficial for the management of critical wounds.

A systematic review of evidence on integrated management of psychiatric disorders in youth who use cannabis.

Given the risks to mental health associated with cannabis use in youth and the increase in cannabis legalization worldwide and in the U.S., there is a need to understand existing evidence-based approaches to integrated management of psychiatric disorders in youth who use cannabis. This systematic review aimed to appraise the current evidence on integrated treatment for adolescents and young adults with common psychiatric disorders who engage in regular cannabis use. A total of 989 studies were screened for inclusion. Study's titles and abstracts were screened and advanced to full text review for further screening by two independent reviewers. Thirty-five full-text articles were reviewed, with five articles ultimately meeting all criteria for inclusion. Five randomized controlled trials examined the effects of therapeutic interventions in youth with common psychiatric disorders who used cannabis, including two studies on depression, one on bipolar disorder, one on anxiety and one on PTSD were reviewed. No studies were considered high in risk of bias. Overall, there is a paucity of research on the treatment of comorbid adolescent mental health disorders and cannabis use, which limits the ability to draw evidence-based treatment recommendations.

Racial Differences in Self-Report of Mental Illness and Mental Illness Treatment in the Community: An Analysis of Jail Intake Data.

Jails and prisons in the United States house people with elevated rates of mental health and substance use disorders. The goal of this cross-sectional study was to evaluate the frequency of racial/ethnic differences in the self-report of mental illness and psychiatric medication use at jail entry. Our sample included individuals who had been incarcerated between 2016 and 2020 at the Middlesex Jail & House of Correction, located in Billerica, MA. We used data from the "Offender Management System," the administrative database used by the jail containing data on people who are incarcerated, and COREMR, the electronic medical record (EMR) used in the Middlesex Jail & House of Correction. We evaluated two primary outcomes (1) self-reported mental illness history and (2) self-reported use of psychiatric medication, with the primary indicator of interest as race/ethnicity. At intake, over half (57%) of the sample self-reported history of mental illness and 20% reported the use of psychiatric medications. Among people who self-reported a history of mental illness, Hispanic (AOR: 0.73, 95% CI: 0.60-0.90), Black (AOR: 0.52, 95% CI: 0.43-0.64), Asian/Pacific Islander (Non-Hispanic) people (AOR: 0.31, 95% CI: 0.13-0.74), and people from other racial/ethnic groups (AOR: 0.33, 95% CI: 0.11-0.93) all had decreased odds of reporting psychiatric medications. Mental illness was reported in about one-half of people who entered jail, but only 20% reported receiving medications in the community prior to incarceration. Our findings build on the existing literature on jail-based mental illness and show racial disparities in self-report of psychiatric medications in people who self-reported mental illness. The timing, frequency, and equity of mental health services in both the community and the jail setting deserves further research, investment, and improvement.

Resolving 500 Years of Anthropogenic Impacts in a Mesotrophic Lake: Nutrients Outweigh Other Drivers of Lake Change.

Interactions among multiple stressors, legacies of past perturbations, and the lack of historical information make it difficult to determine the influence of individual anthropogenic impacts on lakes and separate them from natural ecosystem variability. In the present study, we coupled paleolimnological approaches, historical data, and ecological experiments to disentangle the impacts of multiple long-term stressors on lake ecosystem structure and function. We found that the lake structure and function remained resistant to the impacts of catchment deforestation and erosion, and the introduction of several exotic fish species. Changes in ecosystem structure and function were consistent, with nutrient enrichment being the primary driver of change. Significant and sustained changes in the lake diatom community structure (and their nutrient requirements), bacterial community function, and paleolimnological proxies of ecosystem function coincided with nitrogen and phosphorus fertilizers in the catchment. The results highlight that the effects of increased nutrient inputs are much stronger than the influence of other, potentially significant, drivers of ecosystem change, and that the degree of nutrient impact can be underestimated by environmental monitoring due to its diffuse and accumulative nature. Delineating the effects of multiple anthropogenic drivers requires long-term records of both impacts and lake ecosystem change across multiple trophic levels.

Experiences and Perspectives on Stressors and Organizational Strategies to Bolster Resiliency During the COVID-19 Pandemic: A Qualitative Study of Health Care Workers at a Tertiary Medical Center.

OBJECTIVE: This qualitative study included a sample of health care workers (HCWs) at a tertiary care center providing direct care to patients with COVID-19 to explore experiences and perceptions regarding care delivery during the COVID-19 pandemic as well as factors that helped HCWs cope with the challenges of the pandemic. Methods: Grounded theory methodology was used to conduct virtual focus groups with a semistructured interview guide May to June 2020. Results: We identified major themes related to (1) HCWs' emotions during the pandemic, (2) the perceived triggers of these feelings, (3) organizational factors that made HCWs feel more supported and appreciated, and (4) personal factors that helped HCWs cope with the pandemic. Conclusion: Results highlighted the stress and challenges associated with exposure to SARS-CoV-2. The findings can help inform interventions to support HCWs during pandemics and other crises.

Disparities in Pediatric Mental and Behavioral Health Conditions.

Mental and behavioral health conditions are common among children and adolescents in the United States. The purpose of this state-of the-art review article is to describe inequities in mental and behavioral health care access and outcomes for children and adolescents, characterize mechanisms behind the inequities, and discuss strategies to decrease them. Understanding the mechanisms underlying these inequities is essential to inform strategies to mitigate these health disparities. Half of United States children with a treatable mental health disorder do not receive treatment from a mental health professional. Children and adolescents in racial, ethnic, sexual, sex, and other minority groups experience inequities in access to care and disparities in outcomes for mental and behavioral health conditions. Suicide rates are nearly twice as high in Black compared to White boys 5 to 11 years old and have been increasing disproportionately among adolescent Black girls 12 to 17 years old. Children identifying as a sexual minority have >3 times increased odds of attempting suicide compared to heterosexual peers. Adverse experiences of children living as part of a minority group, including racism and discrimination, have immediate and lasting effects on mental health. Poverty and an uneven geographic distribution of resources also contribute to inequities in access and disparities in outcomes for mental and behavioral health conditions. Strategies to address inequities in mental and behavioral health among United States children include investing in a diverse workforce of mental health professionals, improving access to school-based services, ensuring equitable access to telehealth, and conducting quality improvement with rigorous attention to equity.

Disentangling the influence of microplastics and their chemical additives on a model detritivore system.

Microplastics (MPs) can negatively impact freshwater organisms via physical effects of the polymer itself and/or exposure to chemicals added to plastic during production to achieve desired characteristics. Effects on organisms may result from direct exposure to plastic particles and/or chemical additives or effects may manifest as indirect effects through ecological interactions between organisms (e.g., reduced food availability that impairs a consumer). To disentangle these issues, we used a simplified freshwater food web interaction comprising microbes and macroinvertebrate detritivores to evaluate the toxicity of 1) polyvinyl chloride (PVC) MPs without added chemicals (virgin), 2) the common chemical additive dibutyl phthalate (DBP), and 3) PVC MPs with incorporated DBP. Exposure to virgin PVC MPs (0.33 and 3.3 mg/L) caused negligible ecological effect with the exception of reduced macroinvertebrate feeding rates at 3.3 mg/L. Exposure to DBP (1 mg/L) both individually and when incorporated into the PVC MPs negatively impacted all tested endpoints, including microbial and macroinvertebrate respiration, feeding rate and assimilation efficiency. DBP leached rapidly from the MPs into the water, and also accumulated in macroinvertebrates and their food, providing multiple routes of exposure. Our findings suggest that additives which are intentionally incorporated into MPs could play a key role in MP toxicity and contribute to the disruption of key ecological interactions underpinning ecosystem processes, such as leaf litter decomposition.

Multigenerational exposure to increased temperature reduces metabolic rate but increases boldness in Gambusia affinis.

Acute exposure to warming temperatures increases minimum energetic requirements in ectotherms. However, over and within multiple generations, increased temperatures may cause plastic and evolved changes that modify the temperature sensitivity of energy demand and alter individual behaviors. Here, we aimed to test whether populations recently exposed to geothermally elevated temperatures express an altered temperature sensitivity of metabolism and behavior. We expected that long-term exposure to warming would moderate metabolic rate, reducing the temperature sensitivity of metabolism, with concomitant reductions in boldness and activity. We compared the temperature sensitivity of metabolic rate (acclimation at 20 vs. 30°C) and allometric slopes of routine, standard, and maximum metabolic rates, in addition to boldness and activity behaviors, across eight recently divergent populations of a widespread fish species (Gambusia affinis). Our data reveal that warm-source populations express a reduced temperature sensitivity of metabolism, with relatively high metabolic rates at cool acclimation temperatures and relatively low metabolic rates at warm acclimation temperatures compared to ambient-source populations. Allometric scaling of metabolism did not differ with thermal history. Across individuals from all populations combined, higher metabolic rates were associated with higher activity rates at 20°C and bolder behavior at 30°C. However, warm-source populations displayed relatively bolder behavior at both acclimation temperatures compared to ambient-source populations, despite their relatively low metabolic rates at warm acclimation temperatures. Overall, our data suggest that in response to warming, multigenerational exposure (e.g., plasticity, adaptation) may not result in trait change directed along a simple "pace-of-life syndrome" axis, instead causing relative decreases in metabolism and increases in boldness. Ultimately, our data suggest that multigenerational warming may produce a novel combination of physiological and behavioral traits, with consequences for animal performance in a warming world.

From the Blood-Brain Barrier to Childhood Development: A Case of Acute-Onset Psychosis and Cognitive Impairment Attributed to Systemic Lupus Erythematosus in an Adolescent Female.

LEARNING OBJECTIVES: After participating in this CME activity, the clinician will be better able to:• Interpret classifications of neuropsychiatric systemic lupus erythematosus (NPSLE).• Identify determining factors of neuropsychiatric events.• Analyze current evidence regarding disease pathways for NPSLE.

A bacterial index to estimate lake trophic level: National scale validation.

Lakes and their catchments have been subjected to centuries to millennia of exploitation by humans. Efficient monitoring methods are required to promote proactive protection and management. Traditional monitoring is time consuming and expensive, which limits the number of lakes monitored. Lake surface sediments provide a temporally integrated representation of environmental conditions and contain high microbial biomass. Based on these attributes, we hypothesized that bacteria associated with lake trophic states could be identified and used to develop an index that would not be confounded by non-nutrient stressor gradients. Metabarcoding (16S rRNA gene) was used to assess bacterial communities present in surface sediments from 259 non-saline lakes in New Zealand encompassing a range of trophic states from alpine microtrophic lakes to lowland hypertrophic lakes. A subset of lakes (n = 96) with monitoring data was used to identify indicator amplicon sequence variants (ASVs) associated with different trophic states. A total of 10,888 indicator taxa were identified and used to develop a Sediment Bacterial Trophic Index (SBTI), which signficantly correlated (r2 = 0.842, P < 0.001) with the Trophic Lake Index. The SBTI was then derived for the remaining 163 lakes, providing new knowledge of the trophic state of these unmonitored lakes. This new, robust DNA-based tool provides a rapid and cost-effective method that will allow a greater number of lakes to be monitored and more effectively managed in New Zealand and globally. The SBTI could also be applied in a paleolimnological context to investigate changes in trophic status over centuries to millennia.

Symptoms of Depression and Anxiety Among Black Medical Students: the Role of Peer Connectedness and Perceived Discrimination.

This study examined the association between discrimination, peer connectedness, and mental health symptoms among Black medical students. Data were collected from a convenience sample of Black medical students via an anonymous electronic questionnaire (n = 733) in year 2020. The Patient-Reported Outcomes Measurement Information System Depression and Anxiety forms were used to measure depression and anxiety symptoms. Structural equation modeling was used to examine the association between discrimination, peer connectedness, and mental health symptoms (Mplus 7.3). The majority of the participants were female (80%), approximately 40% were third or fourth year medical school students, and 13% had a clinical diagnosis of depression/anxiety before medical school. About half of the students reported being watched more closely than their classmates, and 66% reported feeling the need to work twice as hard as others to get the same treatment or evaluation. The majority of students reported that their peers were supportive of their academic success (60.7%), and 53% reported that students often or always invited them to social outings. The mean T-score for depressive symptoms was 53.6 (SD = 7.8), and the mean T-score for anxiety symptoms was 58.6 (SD = 8.4). Overall, findings indicated a high prevalence of anxiety and depression symptoms among Black medical students, and increased discrimination was associated with more mental health symptoms among males. Additionally, increased peer connectedness was associated with fewer symptoms of anxiety among males and females and fewer depressive symptoms among females. Addressing discrimination among medical students may improve mental health among Black medical students.

Adolescent Substance Use Disorders.

Adolescent Substance Use DisordersSubstance use disorders contribute to the leading causes of death among adolescents, including homicide and suicide. Here, Simon et al. review the most recent published data on adolescent substance use disorders and the implications for clinical practice.

Towards more ecologically relevant investigations of the impacts of microplastic pollution in freshwater ecosystems.

Microplastic pollution is a major environmental concern and the subject of a rapidly growing body of research. Much of this research has focused on the direct effects of microplastics on single species and there is limited information on how microplastics affect different functional groups of organisms, multi-species interactions, and ecosystem processes. We focused on freshwater systems and reviewed 146 studies of microplastic effects on freshwater biota and recorded features including particle characteristics, study designs, functional types of species tested and ecotoxicological endpoints measured. Study species were categorized based on their ecosystem role/functional feeding group rather than taxonomy. We found that most studies were conducted on single species (95%) and focused on a narrow range of functional groups of organisms (mostly filter feeders, 37% of studies). Very few studies have investigated multi-species interactions and ecosystem processes. In many studies, certain characteristics of microplastics, such as polymer type were not well matched with the feeding and habitat ecology of test species, potentially reducing their ecological relevance. Median laboratory study test concentrations were 5-6 orders of magnitude higher than those reported in the field and few studies considered the effects of chemical additives in plastics (6%). We recommend that studies addressing the ecological effects of microplastics need to address neglected functional groups of organisms, design experiments to better match the ecology of test species, and increase in experimental scale and complexity to identify any indirect effects on species interactions and ecosystem processes. We suggest that examining microplastics through an ecological lens that better integrates the feeding and habitat ecology of test organisms will advance our understanding of the effects microplastics have in the environment.

Synergy between Phage Sb-1 and Oxacillin against Methicillin-Resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) is a notorious pathogen responsible for not only a number of difficult-to-treat hospital-acquired infections, but also for infections that are community- or livestock-acquired. The increasing lack of efficient antibiotics has renewed the interest in lytic bacteriophages (briefly phages) as additional antimicrobials against multi-drug resistant bacteria, including MRSA. The aim of this study was to test the hypothesis that a combination of the well-known and strictly lytic S. aureus phage Sb-1 and oxacillin, which as sole agent is ineffective against MRSA, exerts a significantly stronger bacterial reduction than either antimicrobial alone. Eighteen different MRSA isolates and, for comparison, five MSSA and four reference strains were included in this study. The bacteria were challenged with a combination of varying dosages of the phage and the antibiotic in liquid medium using five different antibiotic levels and four different viral titers (i.e., multiplicity of infections (MOIs) ranging from 10-5 to 10). The dynamics of the cell density changes were determined via time-kill assays over 16 h. Positive interactions between both antimicrobials in the form of facilitation, additive effects, or synergism were observed for most S. aureus isolates. These enhanced antibacterial effects were robust with phage MOIs of 10-1 and 10 irrespective of the antibiotic concentrations, ranging from 5 to 100 µg/mL. Neutral effects between both antimicrobials were seen only with few isolates. Importantly, antagonism was a rare exception. As a conclusion, phage Sb-1 and oxacillin constitute a robust heterologous antimicrobial pair which extends the efficacy of a phage-only approach for controlling MRSA.

Lake microbial communities are not resistant or resilient to repeated large-scale natural pulse disturbances.

Opportunities to study community-level responses to extreme natural pulse disturbances in unaltered ecosystems are rare. Lake sediment records that span thousands of years can contain well-resolved sediment pulses, triggered by earthquakes. These palaeorecords provide a means to study repeated pulse disturbances and processes of resistance (insensitivity to disturbance) and ecological resilience (capacity to regain structure, function and process). In this study, sedimentary DNA was extracted from a sediment core from Lake Paringa (New Zealand) that is situated in a near natural catchment. Metabarcoding and inferred functions were used to assess the lake microbial community over the past 1100 years - a period that included four major earthquakes. Microbial community composition and function differed significantly between highly perturbed (postseismic, ~50 years) phases directly after the earthquakes and more stable (interseismic, ~250 years) phases, indicating a lack of community resistance. Although community structure differed significantly in successive postseismic phases, function did not, suggesting potential functional redundancy. Significant differences in composition and function in successive interseismic phases demonstrate that communities are not resilient to large-scale natural pulse disturbances. The clear difference in structure and function, and high number of indicator taxa (responsible for driving differences in communities between phases) in the fourth interseismic phase probably represents a regime shift, possibly due to the two-fold increase in sediment and terrestrial biospheric organic carbon fluxes recorded following the fourth earthquake. Large pulse disturbances that enhance sediment inputs into lake systems may produce an underappreciated mechanism that destabilises lake ecosystem processes.