Screening for Speech and Language Delay and Disorders in Children 5 Years or Younger: Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Children with speech and language difficulties are at risk for learning and behavioral problems. Objective: To review the evidence on screening for speech and language delay or disorders in children 5 years or younger to inform the US Preventive Services Task Force. Data Sources: PubMed/MEDLINE, Cochrane Library, PsycInfo, ERIC, Linguistic and Language Behavior Abstracts (ProQuest), and trial registries through January 17, 2023; surveillance through November 24, 2023. Study Selection: English-language studies of screening test accuracy, trials or cohort studies comparing screening vs no screening; randomized clinical trials (RCTs) of interventions. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, study quality, and data extraction; results were narratively summarized. Main Outcomes and Measures: Screening test accuracy, speech and language outcomes, school performance, function, quality of life, and harms. Results: Thirty-eight studies in 41 articles were included (N = 9006). No study evaluated the direct benefits of screening vs no screening. Twenty-one studies (n = 7489) assessed the accuracy of 23 different screening tools that varied with regard to whether they were designed to be completed by parents vs trained examiners, and to screen for global (any) language problems vs specific skills (eg, expressive language). Three studies assessing parent-reported tools for expressive language skills found consistently high sensitivity (range, 88%-93%) and specificity (range, 88%-85%). The accuracy of other screening tools varied widely. Seventeen RCTs (n = 1517) evaluated interventions for speech and language delay or disorders, although none enrolled children identified by routine screening in primary care. Two RCTs evaluating relatively intensive parental group training interventions (11 sessions) found benefit for different measures of expressive language skills, and 1 evaluating a less intensive intervention (6 sessions) found no difference between groups for any outcome. Two RCTs (n = 76) evaluating the Lidcombe Program of Early Stuttering Intervention delivered by speech-language pathologists featuring parent training found a 2.3% to 3.0% lower proportion of syllables stuttered at 9 months compared with the control group when delivered in clinic and via telehealth, respectively. Evidence on other interventions was limited. No RCTs reported on the harms of interventions. Conclusions and Relevance: No studies directly assessed the benefits and harms of screening. Some parent-reported screening tools for expressive language skills had reasonable accuracy for detecting expressive language delay. Group parent training programs for speech delay that provided at least 11 parental training sessions improved expressive language skills, and a stuttering intervention delivered by speech-language pathologists reduced stuttering frequency.

A microbial bioherbicide for Striga hermonthica control: production, development, and effectiveness of a seed coating agent.

Witchweed (Striga hermonthica), also called striga, is a parasitic weed that causes high yield losses in maize on more than 200 000 ha in Kenya alone. A new commercial, biological herbicide developed in Kenya is able to control striga effectively. The product was approved for use by the Pest Control Products Board in Kenya in September, 2021. It is self-produced in villages using a secondary inoculum provided by a commercial company. The formulated product has some disadvantages, which are a complicated production process, a very short shelf life and high application rate. Additionally, the product has to be applied manually and therefore can only be used in manual production, leaving out the opportunity for farmers using mechanization. For this reason, efforts have been made to formulate the active ingredient Fusarium oxysporum f. sp. strigae strain DSM 33471, as a powder and to use it as a seed coating agent. This article deals with the production of the Fusarium spore powder, its properties, its application to the seed, and its herbicidal effect demonstrated in the first two field trials. The F. oxysporum strain was originally isolated from a wilting striga plant in Kenya. The strain was virulence enhanced to over produce the amino acids leucine, methionine and tyrosine. These amino acids are responsible for a second mode of action apart from the wilting causing effect of the fungus on striga. Whereas leucine and tyrosine have a herbicidal effect, ethylene from methionine triggers the germination of striga seeds in the soil. Additionally, the strain has been improved to be resistant to the fungicide captan, which is commonly used to treat maize seed in Kenya. Seed coating tests conducted on 25 striga-infested small holder farms spread out in six counties of western Kenya reported yield increases of up to 88%. A second trial carried out by the Kenyan Agricultural and Livestock Research Organization showed a 93% reduction of emerged striga plants. © 2023 Society of Chemical Industry.

The Toothpick Project: commercialization of a virulence-selected fungal bioherbicide for Striga hermonthica (witchweed) biocontrol in Kenya.

The high-level view of global food systems identifies three all-encompassing barriers to the adoption of food systems solutions: knowledge, policy, and finance. These barriers, and the siloed characteristics of each of these, have hindered the development and adoption of microbial herbicides. How knowledge, policy, and finance are related to the Toothpick Project's path of commercializing a new bioherbicide, early in the scope of the industry, is discussed here. The Toothpick Project's innovation, developed over four decades and commercialized in 2021, uses strains of Fusarium oxysporum f.sp. strigae selected for overproduction and excretion of specific amino acids, killing the parasitic weed Striga hermonthica (Striga or witchweed), Africa's worst pest threat to food security. Historically, bioherbicides have not been a sufficient alternative to the dominant use of synthetic chemical herbicides. To be used safely as bioherbicides, plant pathogens need to be host specific, non-toxic, and yet sufficiently virulent to control a specific weed. For commercialization, bioherbicides must be affordable and require a sufficient shelf life for distribution. Given the current triple storm encountered by the chemical herbicide industry (herbicide-resistant weeds, lawsuits, and consumer pushback), there exists an opportunity to use certain plant pathogens as bioherbicides by enhancing their virulence. By discussing barriers in the scope of knowledge, policy, and finance in the development of the Toothpick Project's new microbial bioherbicide, we hope to help others to anticipate the challenges and provide change-leaders, particularly in policy and finance, a ground level perspective of bioherbicide development. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

A qPCR assay for the rapid and specific detection of Shining ram's-horn snail (Segmentina nitida) eDNA from Stodmarsh National Nature Reserve, UK.

Segmentina nitida Müller 1774 is a freshwater snail which was formerly widespread throughout England and south Wales. Since the 1840s it has seen a rapid decline in its range which has been attributed to deteriorating water quality due to nutrient enrichment, lowering of water tables and over-management of the ditches in which it resides. S. nitida has therefore been identified as a UK Biodiversity Action Plan (UKBAP) priority species which recommends further research for its conservation. Here we have developed a Taqman based qPCR eDNA assay for the detection of S. nitida at the Stodmarsh National Nature Reserve and compared the results with a manual survey of the ditches at this location. 32 ditches were surveyed in November 2020 (22 at Stodmarsh) and February 2021 (10 outside the known range of S.nitida). Our eDNA analysis exhibited an observed percentage agreement of 84% with a kappa coefficient of agreement between manual and eDNA surveys of 0.56 (95% CI 0.22 to 0.92). Three ditches determined to be negative for S. nitida by eDNA analysis were manual survey positive, and a further two ditches that were negative by manual survey were positive by eDNA analysis revealing the potential for improved overall detection rates using a combination of manual and eDNA methodologies. eDNA analysis could therefore augment manual survey techniques for S. nitida as a relatively quick and inexpensive tool for collecting presence and distribution data that could be used to inform manual surveys and management of ditches.

An Instrumented Mouthguard for Real-Time Measurement of Head Kinematics under a Large Range of Sport Specific Accelerations.

BACKGROUND: Head impacts in sports can produce brain injuries. The accurate quantification of head kinematics through instrumented mouthguards (iMG) can help identify underlying brain motion during injurious impacts. The aim of the current study is to assess the validity of an iMG across a large range of linear and rotational accelerations to allow for on-field head impact monitoring. METHODS: Drop tests of an instrumented helmeted anthropometric testing device (ATD) were performed across a range of impact magnitudes and locations, with iMG measures collected concurrently. ATD and iMG kinematics were also fed forward to high-fidelity brain models to predict maximal principal strain. RESULTS: The impacts produced a wide range of head kinematics (16-171 g, 1330-10,164 rad/s2 and 11.3-41.5 rad/s) and durations (6-18 ms), representing impacts in rugby and boxing. Comparison of the peak values across ATD and iMG indicated high levels of agreement, with a total concordance correlation coefficient of 0.97 for peak impact kinematics and 0.97 for predicted brain strain. We also found good agreement between iMG and ATD measured time-series kinematic data, with the highest normalized root mean squared error for rotational velocity (5.47 ± 2.61%) and the lowest for rotational acceleration (1.24 ± 0.86%). Our results confirm that the iMG can reliably measure laboratory-based head kinematics under a large range of accelerations and is suitable for future on-field validity assessments.

In-Depth Bicycle Collision Reconstruction: From a Crash Helmet to Brain Injury Evaluation.

Traumatic brain injury (TBI) is a prevalent injury among cyclists experiencing head collisions. In legal cases, reliable brain injury evaluation can be difficult and controversial as mild injuries cannot be diagnosed with conventional brain imaging methods. In such cases, accident reconstruction may be used to predict the risk of TBI. However, lack of collision details can render accident reconstruction nearly impossible. Here, we introduce a reconstruction method to evaluate the brain injury in a bicycle-vehicle collision using the crash helmet alone. Following a thorough inspection of the cyclist's helmet, we identified a severe impact, a moderate impact and several scrapes, which helped us to determine the impact conditions. We used our helmet test rig and intact helmets identical to the cyclist's helmet to replicate the damage seen on the cyclist's helmet involved in the real-world collision. We performed both linear and oblique impacts, measured the translational and rotational kinematics of the head and predicted the strain and the strain rate across the brain using a computational head model. Our results proved the hypothesis that the cyclist sustained a severe impact followed by a moderate impact on the road surface. The estimated head accelerations and velocity (167 g, 40.7 rad/s and 13.2 krad/s2) and the brain strain and strain rate (0.541 and 415/s) confirmed that the severe impact was large enough to produce mild to moderate TBI. The method introduced in this study can guide future accident reconstructions, allowing for the evaluation of TBI using the crash helmet only.

A Review of Cyclist Head Injury, Impact Characteristics and the Implications for Helmet Assessment Methods.

Head injuries are common for cyclists involved in collisions. Such collision scenarios result in a range of injuries, with different head impact speeds, angles, locations, or surfaces. A clear understanding of these collision characteristics is vital to design high fidelity test methods for evaluating the performance of helmets. We review literature detailing real-world cyclist collision scenarios and report on these key characteristics. Our review shows that helmeted cyclists have a considerable reduction in skull fracture and focal brain pathologies compared to non-helmeted cyclists, as well as a reduction in all brain pathologies. The considerable reduction in focal head pathologies is likely to be due to helmet standards mandating thresholds of linear acceleration. The less considerable reduction in diffuse brain injuries is likely to be due to the lack of monitoring head rotation in test methods. We performed a novel meta-analysis of the location of 1809 head impacts from ten studies. Most studies showed that the side and front regions are frequently impacted, with one large, contemporary study highlighting a high proportion of occipital impacts. Helmets frequently had impact locations low down near the rim line. The face is not well protected by most conventional bicycle helmets. Several papers determine head impact speed and angle from in-depth reconstructions and computer simulations. They report head impact speeds from 5 to 16 m/s, with a concentration around 5 to 8 m/s and higher speeds when there was another vehicle involved in the collision. Reported angles range from 10° to 80° to the normal, and are concentrated around 30°-50°. Our review also shows that in nearly 80% of the cases, the head impact is reported to be against a flat surface. This review highlights current gaps in data, and calls for more research and data to better inform improvements in testing methods of standards and rating schemes and raise helmet safety.

Head Impact Location, Speed and Angle from Falls and Trips in the Workplace.

Traumatic brain injury (TBI) is a common injury in the workplace. Trips and falls are the leading causes of TBI in the workplace. However, industrial safety helmets are not designed for protecting the head under these impact conditions. Instead, they are designed to pass the regulatory standards which test head protection against falling heavy and sharp objects. This is likely to be due to the limited understanding of head impact conditions from trips and falls in workplace. In this study, we used validated human multi-body models to predict the head impact location, speed and angle (measured from the ground) during trips, forward falls and backward falls. We studied the effects of worker size, initial posture, walking speed, width and height of the tripping barrier, bracing and falling height on the head impact conditions. Overall, we performed 1692 simulations. The head impact speed was over two folds larger in falls than trips, with backward falls producing highest impact speeds. However, the trips produced impacts with smaller impact angles to the ground. Increasing the walking speed increased the head impact speed but bracing reduced it. We found that 41% of backward falls and 19% of trips/forward falls produced head impacts located outside the region of helmet coverage. Next, we grouped all the data into three sub-groups based on the head impact angle: [0°, 30°], (30°, 60°] and (60°, 90°] and excluded groups with small number of cases. We found that most trips and forward falls lead to impact angles within the (30°, 60°] and (60°, 90°] groups while all backward falls produced impact angles within (60°, 90°] group. We therefore determined five representative head impact conditions from these groups by selecting the 75th percentile speed, mean value of angle intervals and median impact location (determined by elevation and azimuth angles) of each group. This led to two representative head impact conditions for trips: 2.7 m/s at 45° and 3.9 m/s at 75°, two for forward falls: 3.8 m/s at 45° and 5.5 m/s at 75° and one for backward falls: 9.4 m/s at 75°. These impact conditions can be used to improve industrial helmet standards.

Screening for Obstructive Sleep Apnea in Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Obstructive sleep apnea (OSA) is associated with adverse health outcomes. Objective: To review the evidence on screening for OSA in asymptomatic adults or those with unrecognized OSA symptoms to inform the US Preventive Services Task Force. Data Sources: PubMed/MEDLINE, Cochrane Library, Embase, and trial registries through August 23, 2021; surveillance through September 23, 2022. Study Selection: English-language studies of screening test accuracy, randomized clinical trials (RCTs) of screening or treatment of OSA reporting health outcomes or harms, and systematic reviews of treatment reporting changes in blood pressure and apnea-hypopnea index (AHI) scores. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality. Meta-analysis of intervention trials. Main Outcomes and Measures: Test accuracy, excessive daytime sleepiness, sleep-related and general health-related quality of life (QOL), and harms. Results: Eighty-six studies were included (N = 11 051). No study directly compared screening with no screening. Screening accuracy of the Multivariable Apnea Prediction score followed by unattended home sleep testing for detecting severe OSA syndrome (AHI ≥30 and Epworth Sleepiness Scale [ESS] score >10) measured as the area under the curve in 2 studies (n = 702) was 0.80 (95% CI, 0.78 to 0.82) and 0.83 (95% CI, 0.77 to 0.90). Five studies assessing the accuracy of other screening tools were heterogeneous and results were inconsistent. Compared with inactive control, positive airway pressure was associated with a significant improvement in ESS score from baseline (pooled mean difference, -2.33 [95% CI, -2.75 to -1.90]; 47 trials; n = 7024), sleep-related QOL (standardized mean difference, 0.30 [95% CI, 0.19 to 0.42]; 17 trials; n = 3083), and general health-related QOL measured by the 36-Item Short Form Health Survey (SF-36) mental health component summary score change (pooled mean difference, 2.20 [95% CI, 0.95 to 3.44]; 15 trials; n = 2345) and SF-36 physical health component summary score change (pooled mean difference, 1.53 [95% CI, 0.29 to 2.77]; 13 trials; n = 2031). Use of mandibular advancement devices was also associated with a significantly larger ESS score change compared with controls (pooled mean difference, -1.67 [95% CI, 2.09 to -1.25]; 10 trials; n = 1540). Reporting of other health outcomes was sparse; no included trial found significant benefit associated with treatment on mortality, cardiovascular events, or motor vehicle crashes. In 3 systematic reviews, positive airway pressure was significantly associated with reduced blood pressure; however, the difference was relatively small (2-3 mm Hg). Conclusions and Relevance: The accuracy and clinical utility of OSA screening tools that could be used in primary care settings were uncertain. Positive airway pressure and mandibular advancement devices reduced ESS score. Trials of positive airway pressure found modest improvement in sleep-related and general health-related QOL but have not established whether treatment reduces mortality or improves most other health outcomes.

The Molecular Medicine PhD program alumni perceptions of career preparedness.

Over the past two decades, graduate programs have sought to meet the rising need for cross-disciplinary biomedical and translational research training; however, among program evaluation efforts, little is known about student satisfaction with these programs. We report survey results aimed at assessing the overall satisfaction of Molecular Medicine (MolMed) PhD program graduates with their training program and subsequent employment, their research productivity since graduation, and the program elements important for entering their diverse career choices. The survey consisted of quantitative and qualitative instruments and was deployed in June 2020 via email to 45 alumni who had graduated at least two years prior. Investigators assessed mean and median Likert scale data and they conducted a qualitative content analysis on all open-ended narrative survey data using inductive analysis to identify themes. Of the 45 contacted, 26 PhD graduates of the MolMed program responded to the survey. Overall, graduates felt the MolMed curriculum prepared them well for their current career (mean 3.4 out a 4-point Likert scale); and, knowing what they know now, they would likely pursue a PhD degree again (mean 3.7 out of 4). Four overarching themes emerged from the content analysis of the narrative survey data: curriculum and other training experiences; professional skills; importance of a strong advisor/mentor; and, networking and career development. Overall, alumni were satisfied with their MolMed Program experience. They found the curriculum to be strong and relevant, and they believed that it prepared them well for their careers. There may be opportunities to embed additional skills into the curriculum, and the program should continue to offer a strong mentoring and clinical experience, as well as train students for diverse career trajectories.

Screening for Prediabetes and Type 2 Diabetes in Children and Adolescents: Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Of youths diagnosed with type 2 diabetes, many develop microvascular complications by young adulthood. Objective: To review the evidence on benefits and harms of screening children and adolescents for prediabetes and type 2 diabetes to inform the US Preventive Services Task Force (USPSTF). Data Sources: PubMed/MEDLINE, Cochrane Library, and trial registries through May 3, 2021; references; experts; literature surveillance through July 22, 2022. Study Selection: English-language controlled studies evaluating screening or interventions for prediabetes or type 2 diabetes that was screen detected or recently diagnosed. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality; qualitative synthesis of findings. Main Outcomes and Measures: Mortality, cardiovascular morbidity, diabetes-related morbidity, development of diabetes, quality of life, and harms. Results: This review included 8 publications (856 participants; mean age, 14 years [range, 10-17 years]). Of those, 6 were from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. No eligible studies directly evaluated the benefits or harms of screening. One randomized clinical trial (RCT) (TODAY; n = 699 adolescents with obesity; mean age, 14 years) comparing metformin, metformin plus rosiglitazone, and metformin plus lifestyle intervention reported that 2 youths with recently diagnosed diabetes developed kidney impairment (0 vs 1 vs 1, respectively; P > .99) and 11 developed diabetic ketoacidosis (5 vs 3 vs 3, respectively; P = .70). One RCT of 75 adolescents (mean age, 13 years) with obesity with prediabetes compared an intensive lifestyle intervention with standard care and reported that no participants in either group developed diabetes, although follow-up was only 6 months. Regarding harms of interventions, 2 RCTs assessing different comparisons enrolled youths with recently diagnosed diabetes. Major hypoglycemic events were reported by less than 1% of participants. Minor hypoglycemic events were more common among youths treated with metformin plus rosiglitazone than among those treated with metformin or metformin plus lifestyle intervention in TODAY (8.2% vs 4.3% vs 3.4%, P = .05). In 1 study, gastrointestinal adverse events were more commonly reported by those taking metformin than by those taking placebo (abdominal pain: 25% vs 12%; nausea/vomiting: 17% vs 10%; P not reported). Conclusions and Relevance: No eligible studies directly evaluated the benefits or harms of screening for prediabetes and type 2 diabetes in children and adolescents. For youths with prediabetes or recently diagnosed (not screen-detected) diabetes, the only eligible trials reported few health outcomes and found no difference between groups, although evidence was limited by substantial imprecision and a duration of follow-up likely insufficient to assess health outcomes.

The relationship between road traffic collision dynamics and traumatic brain injury pathology.

Road traffic collisions are a major cause of traumatic brain injury. However, the relationship between road traffic collision dynamics and traumatic brain injury risk for different road users is unknown. We investigated 2065 collisions from Great Britain's Road Accident In-depth Studies collision database involving 5374 subjects (2013-20). Five hundred and ninety-five subjects sustained a traumatic brain injury (20.2% of 2940 casualties), including 315 moderate-severe and 133 mild-probable injuries. Key pathologies included skull fracture (179, 31.9%), subarachnoid haemorrhage (171, 30.5%), focal brain injury (168, 29.9%) and subdural haematoma (96, 17.1%). These results were extended nationally using >1 000 000 police-reported collision casualties. Extrapolating from the in-depth data we estimate that there are ∼20 000 traumatic brain injury casualties (∼5000 moderate-severe) annually on Great Britain's roads, accounting for severity differences. Detailed collision investigation allows vehicle collision dynamics to be understood and the change in velocity (known as delta-V) to be estimated for a subset of in-depth collision data. Higher delta-V increased the risk of moderate-severe brain injury for all road users. The four key pathologies were not observed below 8 km/h delta-V for pedestrians/cyclists and 19 km/h delta-V for car occupants (higher delta-V threshold for focal injury in both groups). Traumatic brain injury risk depended on road user type, delta-V and impact direction. Accounting for delta-V, pedestrians/cyclists had a 6-times higher likelihood of moderate-severe brain injury than car occupants. Wearing a cycle helmet during a collision was protective against overall and mild-to-moderate-to-severe brain injury, particularly skull fracture and subdural haematoma. Cycle helmet protection was not due to travel or impact speed differences between helmeted and non-helmeted cyclist groups. We additionally examined the influence of the delta-V direction. Car occupants exposed to a higher lateral delta-V component had a greater prevalence of moderate-severe brain injury, particularly subarachnoid haemorrhage. Multivariate logistic regression models created using total delta-V value and whether lateral delta-V was dominant had the best prediction capabilities (area under the receiver operator curve as high as 0.95). Collision notification systems are routinely fitted in new cars. These record delta-V and automatically alert emergency services to a collision in real-time. These risk relationships could, therefore, inform how routinely fitted automatic collision notification systems alert the emergency services to collisions with a high brain injury risk. Early notification of high-risk scenarios would enable quicker activation of the highest level of emergency service response. Identifying those that require neurosurgical care and ensuring they are transported directly to a centre with neuro-specialist provisions could improve patient outcomes.

Computational prediction of head-ground impact kinematics in e-scooter falls.

E-scooters are the fastest growing mode of micro-mobility with important environmental benefits. However, there are serious concerns about injuries caused by e-scooter accidents. Falls due to poor road surface conditions are a common cause of injury in e-scooter riders, and head injuries are one of the most common and concerning injuries in e-scooter falls. However, the head-ground impact biomechanics in e-scooter falls and its relationship with e-scooter speed and design, road surface conditions and wearing helmets remain poorly understood. To address some of these key questions, we predicted the head-ground impact force and velocity of e-scooter riders in different falls caused by potholes. We used multi-body dynamics approach to model a commercially available e-scooter and simulate 180 falls using human body models. We modelled different pothole sizes to test whether the pothole width and depth influences the onset of falls and head-ground impact velocity and force. We also tested whether the e-scooter travelling speed has an influence on the head-ground impact velocity and force. The simulations were carried out with three human body models to ensure that the results of the study are inclusive of a wide range of rider sizes. For our 10 in. diameter e-scooter wheels, we found a sudden increase in the occurrence of falls when the pothole depth was increased from 3 cm (no falls) to 6 cm (41 falls out of 60 cases). When the falls occurred, we found a head-ground impact force of 13.2 ± 3.4kN, which is larger than skull fracture thresholds. The head-ground impact speed was 6.3 ± 1.4 m/s, which is the same as the impact speed prescribed in bicycle helmet standards. All e-scooter falls resulted in oblique head impacts, with an impact angle of 65 ± 10° (measured from the ground). Decreasing the e-scooter speed reduced the head impact speed. For instance, reducing the e-scooter speed from 30 km/h to 20 km/h led to a 14% reduction in the mean impact speed and 12% reduction in the mean impact force, as predicted by the models. The models also showed that the median male riders were sustaining higher head-ground impact force and speed compared with the small female and large male riders. The findings of this study can assist authorities and e-scooter hiring companies to take more informed actions about road surface conditions and speed limits. These results can also help define representative impact test conditions for assessing the performance of helmets used by e-scooter riders in order to reduce head and brain injuries in e-scooter falls.

Questionnaire-based service evaluation of the efficacy and usefulness of SEREN: a structured education programme for children and young people diagnosed with type 1 diabetes mellitus.

OBJECTIVES: To evaluate the usefulness and effectiveness of a new structured education module for children with type 1 diabetes: Structured Education Reassuring Empowering Nurturing (SEREN) 'Diabetes at Diagnosis'. DESIGN: Retrospective questionnaire-based service evaluation. SETTING: 12/14 paediatric diabetes centres across Wales took part. PARTICIPANTS: Children diagnosed with type 1 diabetes 1 year before (pre-SEREN group) and 1 year after the introduction of SEREN (post-SEREN group) were selected using a national diabetes register. RESOURCE: 'Diabetes at Diagnosis' delivers structured education to empower children and families with self-management of type 1 diabetes. EVALUATION: Primary outcomes were patient-reported effectiveness and user-friendliness of the educational resources and quality of life (PedsQL). Age-appropriate child and parent questionnaires were provided. Clinical outcomes included glycated haemoglobin (HbA1c) at 6 and 12 months, service engagement and diabetes-related hospital admissions in the first year. RESULTS: 89/106 responded pre-SEREN and 108/115 post-SEREN, with no demographic differences at diagnosis. Parent scores for educational package evaluation significantly improved post-SEREN, with a non-significant trend towards improved results in children. PedsQL scores were similar. There was no change in HbA1c overall. Subgroup analyses at 12 months showed a trend towards a lower HbA1c in key stage 1-2 (62 vs 58 mmol/mol, p=0.06) and increased HbA1c in key stage 3-4 (56 vs 66 mmol/mol, p=0.009). There were no differences in hospital admissions or missed clinic appointments. CONCLUSIONS: This is an evaluation of the only standardised type 1 diabetes structured education programme in use for children throughout Wales. This module improved parent-reported outcomes and showed a non-significant trend towards improved usefulness in children, without a difference in a PedsQL scores overall. Ongoing evaluation of the cohort who received subsequent SEREN modules may show the long-term benefit of the programme.

Screening for Prediabetes and Type 2 Diabetes: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Type 2 diabetes is common and is a leading cause of morbidity and disability. Objective: To review the evidence on screening for prediabetes and diabetes to inform the US Preventive Services Task Force (USPSTF). Data Sources: PubMed/MEDLINE, Cochrane Library, and trial registries through September 2019; references; and experts; literature surveillance through May 21, 2021. Study Selection: English-language controlled studies evaluating screening or interventions for prediabetes or diabetes that was screen detected or recently diagnosed. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality; qualitative synthesis of findings; meta-analyses conducted when at least 3 similar studies were available. Main Outcomes and Measures: Mortality, cardiovascular morbidity, diabetes-related morbidity, development of diabetes, quality of life, and harms. Results: The review included 89 publications (N = 68 882). Two randomized clinical trials (RCTs) (25 120 participants) found no significant difference between screening and control groups for all-cause or cause-specific mortality at 10 years. For harms (eg, anxiety or worry), the trials reported no significant differences between screening and control groups. For recently diagnosed (not screen-detected) diabetes, 5 RCTs (5138 participants) were included. In the UK Prospective Diabetes Study, health outcomes were improved with intensive glucose control with sulfonylureas or insulin. For example, for all-cause mortality the relative risk (RR) was 0.87 (95% CI, 0.79 to 0.96) over 20 years (10-year posttrial assessment). For overweight persons, intensive glucose control with metformin improved health outcomes at the 10-year follow-up (eg, all-cause mortality: RR, 0.64 [95% CI, 0.45 to 0.91]), and benefits were maintained longer term. Lifestyle interventions (most involving >360 minutes) for obese or overweight persons with prediabetes were associated with reductions in the incidence of diabetes (23 RCTs; pooled RR, 0.78 [95% CI, 0.69 to 0.88]). Lifestyle interventions were also associated with improved intermediate outcomes, such as reduced weight, body mass index, systolic blood pressure, and diastolic blood pressure (pooled weighted mean difference, -1.7 mm Hg [95% CI, -2.6 to -0.8] and -1.2 mm Hg [95% CI, -2.0 to -0.4], respectively). Metformin was associated with a significant reduction in diabetes incidence (pooled RR, 0.73 [95% CI, 0.64 to 0.83]) and reduction in weight and body mass index. Conclusions and Relevance: Trials of screening for diabetes found no significant mortality benefit but had insufficient data to assess other health outcomes; evidence on harms of screening was limited. For persons with recently diagnosed (not screen-detected) diabetes, interventions improved health outcomes; for obese or overweight persons with prediabetes, interventions were associated with reduced incidence of diabetes and improvement in other intermediate outcomes.

Sex differences in gut microbiota modulation of aversive conditioning, open field activity, and basolateral amygdala dendritic spine density.

Gut microbiota influence numerous aspects of host biology, including brain structure and function. Growing evidence implicates gut microbiota in aversive conditioning and anxiety-related behaviors, but research has focused almost exclusively on males. To investigate whether effects of gut dysbiosis on aversive learning and memory differ by sex, adult female and male C57BL/6N mice were orally administered a moderate dose of nonabsorbable antimicrobial medications (ATMs: neomycin, bacitracin, and pimaricin) or a control over 10 days. Changes in gut microbiome composition were analyzed by 16S rRNA sequencing. Open field behavior, cued aversive learning, context recall, and cued recall were assessed. Following behavioral testing, the morphology of basolateral amygdala (BLA) principal neuron dendrites and spines was characterized. Results revealed that ATMs induced gut dysbiosis in both sexes, with stronger effects in females. ATMs also exerted sex-specific effects on behavior and neuroanatomy. Males were more susceptible than females to microbial modulation of locomotor activity and anxiety-like behavior. Females were more susceptible than males to ATM-induced impairments in aversive learning and cued recall. Context recall remained intact, as did dendritic structure of BLA principal neurons. However, ATMs exerted a sex-specific effect on spine density. A second experiment was conducted to isolate the effects of gut perturbation to cued recall. Extinction was also examined. Results revealed no effect of ATMs on cued recall or extinction, suggesting that gut dysbiosis preferentially impacts aversive learning. These data shed new light on how gut microbiota interact with sex to influence aversive conditioning, open field behavior, and BLA dendritic spine architecture.

Maternal, Fetal, and Child Outcomes of Mental Health Treatments in Women: A Meta-Analysis of Pharmacotherapy.

Objective: The authors systematically reviewed evidence on pharmacotherapy for perinatal mental health disorders. Methods: The authors searched for studies of pregnant, postpartum, or reproductive-age women with mental health disorders treated with pharmacotherapy in MEDLINE, EMBASE, PsycINFO, the Cochrane Library, and trial registries from database inception through June 5, 2020 and surveilled literature through March 2, 2021. Outcomes included symptoms; functional capacity; quality of life; suicidal events; death; and maternal, fetal, infant, or child adverse events. Results: 164 studies were included. Regarding benefits, brexanolone for third-trimester or postpartum depression onset may be associated with improved depressive symptoms at 30 days when compared with placebo. Sertraline for postpartum depression may be associated with improved response, remission, and depressive symptoms when compared with placebo. Discontinuing mood stabilizers during pregnancy may be associated with increased recurrence of mood episodes for bipolar disorder. Regarding adverse events, most studies were observational and unable to fully account for confounding. Evidence on congenital and cardiac anomalies for treatment compared with no treatment was inconclusive. Brexanolone for depression onset in the third trimester or the postpartum period may be associated with risk of sedation or somnolence, leading to dose interruption or reduction when compared with placebo. Conclusions: Evidence from few studies supports the use of pharmacotherapy for perinatal mental health disorders. Although many studies report on adverse events, they could not rule out underlying disease severity as the cause of the association between exposures and adverse events. Patients and clinicians need to make informed, collaborative decisions on treatment choices.

High PD-1/PD-L1 Checkpoint Interaction Infers Tumor Selection and Therapeutic Sensitivity to Anti-PD-1/PD-L1 Treatment.

Many cancers are termed immunoevasive due to expression of immunomodulatory ligands. Programmed death ligand-1 (PD-L1) and cluster of differentiation 80/86 (CD80/86) interact with their receptors, programmed death receptor-1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4), respectively, on tumor-infiltrating leukocytes eliciting immunosuppression. Immunotherapies aimed at blocking these interactions are revolutionizing cancer treatments, albeit in an inadequately described patient subset. To address the issue of patient stratification for immune checkpoint intervention, we quantitatively imaged PD-1/PD-L1 interactions in tumor samples from patients, employing an assay that readily detects these intercellular protein-protein interactions in the less than or equal to 10 nm range. These analyses across multiple patient cohorts demonstrated the intercancer, interpatient, and intratumoral heterogeneity of interacting immune checkpoints. The PD-1/PD-L1 interaction was not correlated with clinical PD-L1 expression scores in malignant melanoma. Crucially, among anti-PD-1-treated patients with metastatic non-small cell lung cancer, those with lower PD-1/PD-L1 interaction had significantly worsened survival. It is surmised that within tumors selecting for an elevated level of PD-1/PD-L1 interaction, there is a greater dependence on this pathway for immune evasion and hence, they exhibit more impressive patient response to intervention. SIGNIFICANCE: Quantitation of immune checkpoint interaction by direct imaging demonstrates that immunotherapy-treated patients with metastatic NSCLC with a low extent of PD-1/PD-L1 interaction show significantly worse outcome.

Early Parenting and the Intergenerational Transmission of Self-Regulation and Behavior Problems in African American Head Start Families.

The present investigation used a national sample of African American Head Start children (N = 640; Mage = 4.40) to determine whether conditions of socioeconomic disadvantage, particularly poverty, low parent education, and single parent homes were associated with children's executive function (EF; attention and impulse control) and behavior problems (internalizing and externalizing symptoms) via the mediating effects of parent-child interactions. Path models with manifest and latent variables revealed that parent-child interactions (i.e., cognitive stimulation, control, and harsh discipline) mediated the association between socioeconomic disadvantage and children's internalizing and externalizing symptoms. Furthermore, parent cognitive stimulation mediated the association between socioeconomic disadvantage and children's EF skills. The overall pattern of results provides empirical support for the family stress model of development in which conditions of socioeconomic disadvantage exert a significant influence on parent-child interactions and in turn children's emergent self-regulation and behavior problems.

Reciprocal Relations Between Maternal Depression and Child Behavior Problems in Families Served by Head Start.

This study used longitudinal cross-lagged modeling to examine reciprocal relations between maternal depression and child behavior problems. Data were drawn from 3,119 children (40% Hispanic, 30% African American, 20% White, and 10% other) from the Family and Child Experiences Survey of 2009 (a nationally representative sample of children served by Head Start). Results documented reciprocal relations between maternal depression and child behavior problems across early childhood (i.e., child age 3-5). Furthermore, the effect of child behavior problems on maternal depression was moderated by child race/ethnicity during children's first year in Head Start, such that the negative effect of child behavior problems on African American mothers' depression was more pronounced compared to Hispanics and other racial/ethnic groups.