Rapid Initiation of Injection Naltrexone for Opioid Use Disorder: A Stepped-Wedge Cluster Randomized Clinical Trial.

Importance: Injectable extended-release (XR)-naltrexone is an effective treatment option for opioid use disorder (OUD), but the need to withdraw patients from opioid treatment prior to initiation is a barrier to implementation. Objective: To compare the effectiveness of the standard procedure (SP) with the rapid procedure (RP) for XR-naltrexone initiation. Design, Setting, and Participants: The Surmounting Withdrawal to Initiate Fast Treatment with Naltrexone study was an optimized stepped-wedge cluster randomized trial conducted at 6 community-based inpatient addiction treatment units. Units using the SP were randomly assigned at 14-week intervals to implement the RP. Participants admitted with OUD received the procedure the unit was delivering at the time of their admission. Participant recruitment took place between March 16, 2021, and July 18, 2022. The last visit was September 21, 2022. Interventions: Standard procedure, based on the XR-naltrexone package insert (approximately 5-day buprenorphine taper followed by a 7- to 10-day opioid-free period and RP, defined as 1 day of buprenorphine at minimum necessary dose, 1 opioid-free day, and ascending low doses of oral naltrexone and adjunctive medications (eg, clonidine, clonazepam, antiemetics) for opioid withdrawal. Main Outcomes and Measures: Receipt of XR-naltrexone injection prior to inpatient discharge (primary outcome). Secondary outcomes included opioid withdrawal scores and targeted safety events and serious adverse events. All analyses were intention-to-treat. Results: A total of 415 participants with OUD were enrolled (mean [SD] age, 33.6 [8.48] years; 205 [49.4%] identified sex as male); 54 [13.0%] individuals identified as Black, 91 [21.9%] as Hispanic, 290 [69.9%] as White, and 22 [5.3%] as multiracial. Rates of successful initiation of XR-naltrexone among the RP group (141 of 225 [62.7%]) were noninferior to those of the SP group (68 of 190 [35.8%]) (odds ratio [OR], 3.60; 95% CI, 2.12-6.10). Withdrawal did not differ significantly between conditions (proportion of days with a moderate or greater maximum Clinical Opiate Withdrawal Scale score (>12) for RP vs SP: OR, 1.25; 95% CI, 0.62-2.50). Targeted safety events (RP: 12 [5.3%]; SP: 4 [2.1%]) and serious adverse events (RP: 15 [6.7%]; SP: 3 [1.6%]) were infrequent but occurred more often with RP than SP. Conclusions and Relevance: In this trial, the RP of XR-naltrexone initiation was noninferior to the standard approach and saved time, although it required more intensive medical management and safety monitoring. The results of this trial suggest that rapid initiation could make XR-naltrexone a more viable treatment for patients with OUD. Trial Registration: ClinicalTrials.gov Identifier: NCT04762537.

Older adults at greater risk for Alzheimer's disease show stronger associations between sleep apnea severity in REM sleep and verbal memory.

BACKGROUND: Obstructive sleep apnea (OSA) increases risk for cognitive decline and Alzheimer's disease (AD). While the underlying mechanisms remain unclear, hypoxemia during OSA has been implicated in cognitive impairment. OSA during rapid eye movement (REM) sleep is usually more severe than in non-rapid eye movement (NREM) sleep, but the relative effect of oxyhemoglobin desaturation during REM versus NREM sleep on memory is not completely characterized. Here, we examined the impact of OSA, as well as the moderating effects of AD risk factors, on verbal memory in a sample of middle-aged and older adults with heightened AD risk. METHODS: Eighty-one adults (mean age:61.7 ± 6.0 years, 62% females, 32% apolipoprotein E ε4 allele (APOE4) carriers, and 70% with parental history of AD) underwent clinical polysomnography including assessment of OSA. OSA features were derived in total, NREM, and REM sleep. REM-NREM ratios of OSA features were also calculated. Verbal memory was assessed with the Rey Auditory Verbal Learning Test (RAVLT). Multiple regression models evaluated the relationships between OSA features and RAVLT scores while adjusting for sex, age, time between assessments, education years, body mass index (BMI), and APOE4 status or parental history of AD. The significant main effects of OSA features on RAVLT performance and the moderating effects of AD risk factors (i.e., sex, age, APOE4 status, and parental history of AD) were examined. RESULTS: Apnea-hypopnea index (AHI), respiratory disturbance index (RDI), and oxyhemoglobin desaturation index (ODI) during REM sleep were negatively associated with RAVLT total learning and long-delay recall. Further, greater REM-NREM ratios of AHI, RDI, and ODI (i.e., more events in REM than NREM) were related to worse total learning and recall. We found specifically that the negative association between REM ODI and total learning was driven by adults 60 + years old. In addition, the negative relationships between REM-NREM ODI ratio and total learning, and REM-NREM RDI ratio and long-delay recall were driven by APOE4 carriers. CONCLUSION: Greater OSA severity, particularly during REM sleep, negatively affects verbal memory, especially for people with greater AD risk. These findings underscore the potential importance of proactive screening and treatment of REM OSA even if overall AHI appears low.

The impact of critical thinking skills on student pharmacist GPA at a historically Black university.

INTRODUCTION: Limited information is available regarding whether malleable factors such as critical thinking skills are associated with academic performance among underrepresented minority pharmacy students. This study assessed the relationship between critical thinking skills and grade point average (GPA) among pharmacy students attending a Historically Black College. METHODS: A cross sectional study design was utilized to evaluate the association between student's GPA and critical thinking skills. Demographic data and GPA were abstracted from student records. The health sciences reasoning test with numeracy was administered to pharmacy students at Howard University during the 2017 to 2018 academic year. Critical thinking scores were classified as weak, moderate, or strong/superior. A one way analysis of variance was conducted to ascertain if the average GPA differed based on critical thinking skills category. A multiple linear regression analysis was conducted to determine whether student's critical thinking skill category was associated with the cumulative GPA after accounting for other factors. RESULTS: Among 217 students, the mean GPA among students with a weak critical thinking skills score (3.22 ± 0.40) was lower compared to students with a strong/superior score (3.39 ± 0.33) with a p-value of 0.029. After adjusting for other factors, a strong/superior critical thinking skills score was associated with a higher GPA (p-value = 0.024) in comparison to weak critical thinking skills. CONCLUSION: Stronger critical thinking skills scores are associated with better academic performance among underrepresented minority pharmacy students.

Identification of prognostic factors for survival in patients with metastatic gastric adenocarcinoma in a Mexican population.

INTRODUCTION AND AIMS: Gastric adenocarcinoma is among the high-ranking tumors, with respect to frequency and mortality, worldwide. The inflammatory process and immune system activity are associated with oncologic control. Our aim was to identify whether the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and other variables are prognostic factors for survival in patients with metastatic gastric cancer in a Mexican population. MATERIAL AND METHODS: Patients diagnosed with metastatic gastric adenocarcinoma, hospitalized within the time frame of December 2011 to 2021, were analyzed. The NLR, PLR, and albumin and hemoglobin levels obtained from blood samples were calculated. Functional status (ECOG and Karnofsky), sex, histology, and the presence of signet ring cells were also considered possible prognostic factors. Each factor's prognostic value for overall survival was determined through univariate and multivariate analyses. RESULTS: The study included 956 patients diagnosed with metastatic gastric cancer, of whom 494 (51.7%) were men and 462 (48.3%) were women. The main histologic finding was diffuse adenocarcinoma (n = 619, 64.7%), followed by intestinal adenocarcinoma (n = 293, 30.6%), and the presence of signet ring cells was found in 659 (68.9%) patients. Diagnostic laparoscopy was performed on 238 patients (24.9%) to confirm peritoneal carcinomatosis. The multivariate analysis showed that an NLR above 3.2 (HR 1.51, 95% CI 1.27-1.8; p < 0.001), albumin below 3.5 g/dl (HR 1.25, CI 1.06-1.47; p = 0.006), and an ECOG performance status of 2 or higher (HR 1.39, CI 1.10-1.76; p = 0.005) were independent factors that predicted a lower survival rate, whereas a Karnofsky score above 70% (HR 0.69, CI 0.53-0.91; p = 0.008) was associated with a better survival rate. Lastly, the PLR was not statistically significant in the multivariate analysis. CONCLUSIONS: The NLR, nutritional status assessed through albumin measurement, and functional status can act as independent prognostic survival factors in hospitalized Mexican patients diagnosed with metastatic gastric adenocarcinoma and be taken into account during therapeutic decision-making.

Cerebrovascular pathology mediates associations between hypoxemia during rapid eye movement sleep and medial temporal lobe structure and function in older adults.

Obstructive sleep apnea (OSA) is common in older adults and is associated with medial temporal lobe (MTL) degeneration and memory decline in aging and Alzheimer's disease (AD). However, the underlying mechanisms linking OSA to MTL degeneration and impaired memory remains unclear. By combining magnetic resonance imaging (MRI) assessments of cerebrovascular pathology and MTL structure with clinical polysomnography and assessment of overnight emotional memory retention in older adults at risk for AD, cerebrovascular pathology in fronto-parietal brain regions was shown to statistically mediate the relationship between OSA-related hypoxemia, particularly during rapid eye movement (REM) sleep, and entorhinal cortical thickness. Reduced entorhinal cortical thickness was, in turn, associated with impaired overnight retention in mnemonic discrimination ability across emotional valences for high similarity lures. These findings identify cerebrovascular pathology as a contributing mechanism linking hypoxemia to MTL degeneration and impaired sleep-dependent memory in older adults.

The psychiatric-mental health nurse practitioner as coordinating practitioner in the Netherlands: A multiple case study.

BACKGROUND: Psychiatric-mental health nurse practitioners (PMHNPs) in the Netherlands have been allowed to perform the role of coordinating practitioner (CP) since 2018. This role is reserved for mental health care specialists who are trained and qualified at the master's degree level. Earlier studies have not addressed how PMHNPs perform that role and what mechanisms and contextual factors determine their performance. This understanding could help optimize their performance in this role and promote effective deployment of PMHNPs in mental health care. PURPOSE: To understand how PMHNPs perform this role and what mechanisms and contextual factors underlie that performance. METHODOLOGY: A multiple case study involving PMHNPs who work in various settings as CPs. Data were collected and analyzed using the realistic evaluation approach. RESULTS: We identified four mechanisms related to the performance of PMHNPs in the role of CP: (1) autonomous performance; (2) unique expertise; (3) accessibility, availability, and professional involvement; and (4) additional roles. The extent to which these mechanisms are present is largely determined by organizational factors, team factors, and individual factors. CONCLUSIONS: Psychiatric-mental health nurse practitioners are seeking to identify and interpret the role of CP. This study helps to elucidate the mechanism of role performance by PMHNPs and what they should focus on to deliver effective and patient-centered mental health care. IMPLICATIONS: Policymakers, health care professionals, and educators should consider the mechanisms and contextual factors to facilitate and support PMHNPs' employment and training in the role of CP.

Preservation of the inferior alveolar vasculonervous bundle in mandibular resective therapies: systematic review and report of two cases.

BACKGROUND: Segmental surgical resection is a frequently indicated procedure to treat aggressive mandibular tumors. One of the most important complications derived from this technique is permanent paresthesia of the inferior alveolar nerve (IAN), which significantly affects the quality of life of patients who experience it. This could be avoided through maneuvers that preserve the IAN. The objective of this paper is to review the main techniques for IAN preservation and to present 2 cases with the technique used by the author. MATERIAL AND METHODS: A systematic review was performed according to the PRISMA guidelines, apropos of two clinical cases reported in this study. The MEDLINE/PubMed and Scopus databases were searched. Several variables were considered and are presented in detail in the form of tables and figures. In addition, 2 case reports with NAI preservation techniques are presented. RESULTS: 13 articles were finally obtained for analysis. 127 patients were evaluated, reporting mandibular resections associated with various pathologies. Various surgical techniques were used, all with the same goal of maintaining the IAN. In most of the patients, the maintenance of sensitivity was achieved, which was verified with different methods. CONCLUSIONS: Preservation of the IAN in maxillofacial surgical procedures where surgical resection of the mandibular bone has been performed is an alternative that has demonstrated successful results in terms of reducing postoperative sequelae and is currently positioned as a necessary and feasible procedure.

New complementary alternatives in third molar autotransplantation: A systematic review.

BACKGROUND: Dental autotransplantation (DAT) is defined as the replacement or direct transfer of an impacted, semi-impacted or erupted tooth to a donor site, either to a post-extraction socket or to a surgically created socket within the same individual. The use of new technological advances, such as 3-D dental models based on computer-aided design, among others, have been reported to improve the success rate of DAT. Therefore, we aimed to perform a systematic review to explore the possible benefits that the use of these innovative techniques can provide when applied to DAT. MATERIAL AND METHODS: The literature search was conducted in PubMed, Scopus, and Web of Science databases following the PRISMA guidelines. The research question was: "Are computerized technological advancements a useful tool for improving the success of third molar autotransplantation technique? RESULTS: The initial literature search identified 195 articles, of which only 11 were included for qualitative analysis. All studies used 3D dental models based on computer-aided design data. Surgical guides and stereolithographic models were used by 4 and 1 study respectively. A total of 91 transplanted teeth were evaluated, out of which only 88 were considered within the parameters of clinical success (96.7%). Only 7 out of the 11 articles reported the specific autotransplanted tooth, being mandibular third molars the most prevalent autotransplanted teeth. CONCLUSIONS: Although the application of new technologies for DAT increases the success rate of this technique, further primary studies are still needed to address long-term teeth survival rates and complications. The cost and availability to implement the integration of these techniques to DAT may be a variable to consider, as this can be a limitation for some patients or for low-income countries.

Exploring a syndemic of poverty, cumulative violence, and HIV vulnerability among refugee youth: multi-method insights from a humanitarian setting in Uganda.

Synergistic associations between social inequities and HIV vulnerabilities - known as a syndemic - are understudied with youth in humanitarian settings. We explored refugee youths' HIV prevention needs in Bidi Bidi Refugee Settlement, Uganda. This multi-methods study involved 6 focus groups and 12 in-depth individual interviews (IDI) with refugee youth (n = 60) aged 16-24, and IDI with refugee elders (n = 8) and healthcare providers (n = 8). We then conducted cross-sectional surveys with refugee youth (16-24 years) (n = 115) to assess: poverty, recent sexual and gender-based violence (SGBV), and condom engagement motivation (CEM) (wanting to learn about condoms for HIV prevention). Multivariable logistic regression was used to estimate adjusted odds ratios for associations between poverty and SGBV with CEM. Qualitative narratives revealed poverty and trauma elevated substance use, and these converged to exacerbate SGBV. SGBV and transactional sex increased HIV vulnerabilities. Among survey participants, poverty and recent SGBV were associated with reduced odds of CEM. The interaction between poverty and recent SGBV was significant: the predicted probability of CEM among youth who experienced both poverty and SGBV was almost half than among youth who experienced poverty alone, SGBV alone, or neither. Findings signal the confluence of poverty, violence, and substance use elevate refugee youth HIV vulnerabilities.

Cardiorespiratory fitness and circadian rhythms in adolescents: a pilot study.

Although cardiorespiratory fitness (CRF), an important marker of youth health, is associated with earlier sleep/wake schedule, its relationship with circadian rhythms is unclear. This study examined the associations between CRF and rhythm variables in adolescents. Eighteen healthy adolescents (10 females and 8 males; Mage = 14.6 ± 2.3 yr) completed two study visits on weekdays bracketing an ambulatory assessment during summer vacation. Visit 1 included in-laboratory CRF assessment (peak V̇o2) using a ramp-type progressive cycle ergometry protocol and gas exchange measurement, which was followed by 7-14 days of actigraphy to assess sleep/wake patterns and 24-h activity rhythms. During Visit 2, chronotype, social jetlag (i.e., the difference in midsleep time between weekdays and weekends), and phase preference were assessed using a questionnaire, and hourly saliva samples were collected to determine the dim light melatonin onset (DLMO) phase. All analyses were adjusted for sex, pubertal status, and physical activity. Greater peak V̇o2 was associated with earlier sleep/wake times and circadian phase measures, including acrophase, UP time, DOWN time, last activity peak (LAP) time, and chronotype (all P < 0.05). Peak V̇o2 was negatively associated with social jetlag (P = 0.02). In addition, the mixed-model analysis revealed a significant interaction effect between peak V̇o2 and actigraphy-estimated hour-by-hour activity patterns (P < 0.001), with the strongest effects observed at around the time of waking (0600-1000). In healthy adolescents, better CRF was associated with an earlier circadian phase and increased activity levels notably during the morning. Future studies are needed to investigate the longitudinal effects of the interactions between CRF and advanced rhythms on health outcomes.NEW & NOTEWORTHY In healthy adolescents, better cardiorespiratory fitness, as assessed by the gold standard measure [laboratory-based assessment of peak oxygen consumption (V̇o2)], was associated with earlier circadian timing of sleep/wake patterns, rest-activity rhythms and chronotype, and less social jetlag. These findings highlight the close interrelationships between fitness and rhythms and raise the possibility that maintaining higher cardiorespiratory fitness levels alongside earlier sleep/wake schedule and activity rhythms may be important behavioral intervention targets to promote health in adolescents.

Associations between human milk oligosaccharides and infant growth in a Bangladeshi mother-infant cohort.

BACKGROUND: We aimed to estimate associations between human milk oligosaccharides (HMOs) and infant growth (length-for-age (LAZ) and weight-for-length (WLZ) z-scores) at 12 months postnatal age. METHODS: In this secondary analysis of data from a maternal vitamin D trial in Dhaka, Bangladesh (N = 192), absolute concentrations of HMOs were measured in 13 ± 1 week(s) postpartum milk samples, infant anthropometric measurements were obtained soon after birth and at 12 months postpartum, and infant feeding was classified during 6 months postpartum. Associations between individual HMOs or HMO groups and LAZ or WLZ were estimated by multivariable linear regression adjusting for infant feeding pattern, maternal secretor status, and other potential confounders. RESULTS: The concentrations of 6'sialyllactose, lacto-N-neotetraose, and the non-fucosylated non-sialylated HMOs were inversely associated with LAZ at 12 months of age, whereas the fucosylated non-sialylated HMO concentration was positively associated with LAZ at 12 months. These associations were robust in analyses restricted to infants who were primarily exclusively/predominantly fed human milk during the first 3 (or 6) months. CONCLUSIONS: Since HMOs are both positively and negatively associated with postnatal growth, there is a need for randomized trials to estimate the causal benefits and risks of exogenously administered HMOs on infant growth and other health outcomes. IMPACT: 6'sialyllactose, lacto-N-neotetraose, and the non-fucosylated non-sialylated human milk oligosaccharides (HMOs) were inversely associated with length-for-age z-scores (LAZ) at 12 months, whereas the fucosylated non-sialylated HMO concentration was positively associated with LAZ at 12 months among Bangladeshi infants. Associations between individual and grouped HMOs with infant length growth at 12 months were as strong or stronger in analyses restricted to infants who were exclusively or predominantly fed human milk up to 3 (or 6) months. Randomized trials are needed to characterize the effects of specific HMOs on infant growth, particularly in countries where postnatal linear growth faltering is common.

Examining the diagnostic value of the mnemonic discrimination task for classification of cognitive status and amyloid-beta burden.

Alzheimer's disease (AD) is the most common type of dementia, characterized by early memory impairments and gradual worsening of daily functions. AD-related pathology, such as amyloid-beta (Aß) plaques, begins to accumulate many years before the onset of clinical symptoms. Predicting risk for AD via related pathology is critical as the preclinical stage could serve as a therapeutic time window, allowing for early management of the disease and reducing health and economic costs. Current methods for detecting AD pathology, however, are often expensive and invasive, limiting wide and easy access to a clinical setting. A non-invasive, cost-efficient platform, such as computerized cognitive tests, could be potentially useful to identify at-risk individuals as early as possible. In this study, we examined the diagnostic value of an episodic memory task, the mnemonic discrimination task (MDT), for predicting risk of cognitive impairment or Aß burden. We constructed a random forest classification algorithm, utilizing MDT performance metrics and various neuropsychological test scores as input features, and assessed model performance using area under the curve (AUC). Models based on MDT performance metrics achieved classification results with an AUC of 0.83 for cognitive status and an AUC of 0.64 for Aß status. Our findings suggest that mnemonic discrimination function may be a useful predictor of progression to prodromal AD or increased risk of Aß load, which could be a cost-efficient, noninvasive cognitive testing solution for potentially wide-scale assessment of AD pathological and cognitive risk.

Medial temporal lobe functional network architecture supports sleep-related emotional memory processing in older adults.

Memory consolidation occurs via reactivation of a hippocampal index during non-rapid eye movement slow-wave sleep (NREM SWS) which binds attributes of an experience existing within cortical modules. For memories containing emotional content, hippocampal-amygdala dynamics facilitate consolidation over a sleep bout. This study tested if modularity and centrality-graph theoretical measures that index the level of segregation/integration in a system and the relative import of its nodes-map onto central tenets of memory consolidation theory and sleep-related processing. Findings indicate that greater network integration is tied to overnight emotional memory retention via NREM SWS expression. Greater hippocampal and amygdala influence over network organization supports emotional memory retention, and hippocampal or amygdala control over information flow are differentially associated with distinct stages of memory processing. These centrality measures are also tied to the local expression and coupling of key sleep oscillations tied to sleep-dependent memory consolidation. These findings suggest that measures of intrinsic network connectivity may predict the capacity of brain functional networks to acquire, consolidate, and retrieve emotional memories.

The schistosomicidal activity of ethanolic extracts from branches, leaves, flowers and fruits of Handroanthus impetiginosus (Mart. ex DC.) Mattos (Bignoniaceae) plant and metabolic profile characterization by UPLC-ESI-QTOF analysis.

Schistosomiasis, caused by Schistosoma mansoni Sambon, 1907, is a severe and widely distributed parasitic disease, affecting about 200 million people worldwide. The disease is recognized by elevated mortality rates, especially among those living in areas of poor sanitation. Currently, the chemotherapeutic treatment is solely based on using the praziquantel drug. Therefore, there is a need for the discovery of new medicines for the treatment of this parasitosis. Thus, this work aimed to evaluate the schistosomicidal activity of ethanolic crude extracts from the branches, leaves, flowers, and fruits of Handroanthus impetiginosus (Mart ex DC.) Masttos and characterize its metabolic profile by UPLC-ESI-QTOF analysis. Evaluation of plant extract on S. mansoni was carried out in adult worms in vitro, in which the mortality rate was quantified, and the damages in the tegument of the worms were monitored. All extracts induced changes in the viability of adult males of S. mansoni, causing the death of the parasites, which was directly dependent of the concentration.

Distinct trajectories of caregiver-toddler physiological attunement during routine vaccinations.

Introduction: Toddlers rely on their caregivers for regulatory support when faced with pain-related distress. The caregiver's ability to support their toddler relies on their capacity to regulate their own distress and respond effectively to the child's need for support. The aim of the current study was to describe patterns of caregiver-toddler physiological co-regulatory patterns, also known as attunement, during routine vaccinations across the second year of life. Methods: Caregiver-toddler dyads (N = 189) were part of a longitudinal cohort observed at either 12-, 18-, or 24-month well-baby vaccinations. Parallel-process growth-mixture modeling was used to examine patterns of dyadic physiological co-regulatory responses, indexed by high-frequency heart rate variability (HF-HRV). Results: Three groups of dyads were discerned. The largest group (approximately 80%) demonstrated physiological attunement, with a stable and parallel regulatory pattern of HF-HRV from baseline to postneedle. The second group (7.9%) had parallel regulatory trajectories but with notably lower (ie, less regulated) HF-HRV values, which indicates independent regulatory responses (ie, a lack of attunement among dyad members). The third group (11.1%) showed diverging regulatory trajectories: Caregivers showed a stable regulatory trajectory, but toddlers demonstrated a steep decrease followed by an increase in HF-HRV values that surpassed their baseline levels by the third minute postneedle. Post hoc analyses with the HF-HRV groupings explored heart rate patterns and potential predictors. Conclusions: These findings elucidate potential adaptive and maladaptive co-regulatory parasympathetic patterns in an acute pain context.

Functional network structure supports resilience to memory deficits in cognitively normal older adults with amyloid-ß pathology.

Older adults may harbor large amounts of amyloid-ß (Aß) pathology, yet still perform at age-normal levels on memory assessments. We tested whether functional brain networks confer resilience or compensatory mechanisms to support memory in the face of Aß pathology. Sixty-five cognitively normal older adults received high-resolution resting state fMRI to assess functional networks, 18F-florbetapir-PET to measure Aß, and a memory assessment. We characterized functional networks with graph metrics of local efficiency (information transfer), modularity (specialization of functional modules), and small worldness (balance of integration and segregation). There was no difference in functional network measures between older adults with high Aß (Aß+) compared to those with no/low Aß (Aß-). However, in Aß+ older adults, increased local efficiency, modularity, and small worldness were associated with better memory performance, while this relationship did not occur Aß- older adults. Further, the association between increased local efficiency and better memory performance in Aß+ older adults was localized to local efficiency of the default mode network and hippocampus, regions vulnerable to Aß and involved in memory processing. Our results suggest functional networks with modular and efficient structures are associated with resilience to Aß pathology, providing a functional target for intervention.

Effect of Fenton process as a pretreatment in the phytoremediation of metronidazole by Scirpus lacustris.

The present study evaluated the effect of the Fenton process as pretreatment for metronidazole (MNZ) removal coupled with a phytoremediation system using Scirpus lacustris as macrophyte. Initial concentrations of 0.5, 5, 10, 15, and 20 mg MNZ/L were studied in batch cultures. Results obtained in the MNZ removal by phytoremediation showed efficiencies of 93 ± 2%, 81 ± 4%, 85 ± 1%, 84 ± 2%, and 87 ± 6%, respectively. The metronidazole pretreated by the Fenton process and subsequently fed to the phytoremediation system increased the removal efficiencies up to 93 ± 3%, 99 ± 1%, 99 ± 4%, 94 ± 2%, and 94 ± 3%, respectively. Individual studies with Scirpus lacustris in touch with metronidazole displayed relative growth rates of 0.02-0.04 d-1, showing the not toxic effect of the antibiotic on the macrophyte growth. On the other hand, the BMG kinetic model best describes the removal of MNZ by phytoremediation. Finally, applying the Fenton process as a pretreatment makes the MNZ more assimilable for the phytoremediation system, converting the integration of Fenton with the phytoremediation like other attractive technology to be considered in removing emerging compounds.

The influence of government policies on the nurse practitioner and physician assistant workforce in the Netherlands, 2000-2022: a multimethod approach study.

BACKGROUND: Many countries are looking for ways to increase nurse practitioner (NP) and physician assistant/associate (PA) deployment. Countries are seeking to tackle the pressing issues of increasing healthcare demand, healthcare costs, and medical doctor shortages. This article provides insights into the potential impact of various policy measures on NP/PA workforce development in the Netherlands. METHODS: We applied a multimethod approach study using three methods: 1) a review of government policies, 2) surveys on NP/PA workforce characteristics, and 3) surveys on intake in NP/PA training programs. RESULTS: Until 2012, the annual intake into NP and PA training programs was comparable to the number of subsidized training places. In 2012, a 131% increase in intake coincided with extending the legal scope of practice of NPs and PAs and substantially increasing subsidized NP/PA training places. However, in 2013, the intake of NP and PA trainees decreased by 23% and 24%, respectively. The intake decreased in hospitals, (nursing) home care, and mental healthcare, coinciding with fiscal austerity in these sectors. We found that other policies, such as legal acknowledgment, reimbursement, and funding platforms and research, do not consistently coincide with NP/PA training and employment trends. The ratios of NPs and PAs to medical doctors increased substantially in all healthcare sectors from 3.5 and 1.0 per 100 full-time equivalents in medical doctors in 2012 to 11.0 and 3.9 in 2022, respectively. For NPs, the ratios vary between 2.5 per 100 full-time equivalents in medical doctors in primary care and 41.9 in mental healthcare. PA-medical doctor ratios range from 1.6 per 100 full-time equivalents in medical doctors in primary care to 5.8 in hospital care. CONCLUSIONS: This study reveals that specific policies coincided with NP and PA workforce growth. Sudden and severe fiscal austerity coincided with declining NP/PA training intake. Furthermore, governmental training subsidies coincided and were likely associated with NP/PA workforce growth. Other policy measures did not consistently coincide with trends in intake in NP/PA training or employment. The role of extending the scope of practice remains to be determined. The skill mix is shifting toward an increasing share of medical care provided by NPs and PAs in all healthcare sectors.

Parents' physiological reactivity to child distress and associations with parenting behaviour: A systematic review.

This systematic review and narrative synthesis characterized parents' physiological stress responses to child distress and how parents' physiological and behavioural responses relate. The review was pre-registered with PROSPERO (#CRD42021252852). In total, 3607 unique records were identified through Medline, Embase, PsycINFO, and CINAHL. Fifty-five studies reported on parents' physiological stress responses during their young child's (0-3 years) distress and were included in the review. Results were synthesized based on the biological outcome and distress context used and risk of bias was evaluated. Most studies examined cortisol or heart rate variability (HRV). Small to moderate decreases in parents' cortisol levels from baseline to post-stressor were reported across studies. Studies of salivary alpha amylase, electrodermal activity, HRV, and other cardiac outcomes reflected weak or inconsistent physiological responses or a paucity of relevant studies. Among the studies that examined associations between parents' physiological and behavioural responses, stronger associations emerged for insensitive parenting behaviours and during dyadic frustration tasks. Risk of bias was a significant limitation across studies and recommendations for future research are discussed.

Caregiver and Child Distress as Predictors of Dyadic Physiological Attunement During Vaccination.

OBJECTIVE: Previous research discerned 3 groups of caregiver-toddler dyads that differed in their physiological coregulatory patterns, also known as physiological attunement, during routine vaccinations in the second year of life. One group of dyads (80% of sample) displayed an attuned regulatory pattern, and 2 groups of dyads (20% of sample) showed maladaptive attunement patterns (ie, a lack of attunement or misattunement). The objective of the current study was to examine how well the pain-related distress of children and caregivers during vaccination predicted these patterns. METHODS: Caregiver-toddler dyads (N = 189) were part of a longitudinal cohort observed at either 12-, 18-, or 24-month vaccination appointments. The caregiver's self-report of worry was assessed before and after the needle, and the child behavioral pain-related distress was also measured during the vaccination appointment. Logistic regression was used to determine how well these variables predicted caregiver-child physiological attunement patterns, as indexed by high-frequency heart rate variability. RESULTS: Higher behavioral pain-related distress at various timepoints after the needle were associated with membership in the dyad groups that showed misattunement or lack of attunement. Further, caregivers with higher preneedle worry and lower postneedle worry had a greater likelihood of belonging to groups that showed a maladaptive attunement pattern. DISCUSSION: Findings suggest that caregivers who experience distress associated with their toddlers' vaccination experience more difficulty coregulating with their child during vaccination, and these children are at risk of experiencing higher levels of pain-related distress. This research highlights the need to help caregivers support their children's regulation during vaccination.