Towards system redesign: An exploratory analysis of neurodivergent traits in a childhood population referred for autism assessment

by Jason Lang, Georgia Wylie, Caroline Haig, Christopher Gillberg, Helen Minnis

Background

Children’s health services in many countries are moving from single condition diagnostic silo assessments to considering neurodevelopment in a more holistic sense. There has been increasing recognition of the importance of clinical overlap and co-occurrence of different neurotypes when assessing neurodivergent children. Using a cross-sectional service evaluation design, we investigated the overlap of neurodivergences in a cohort of children referred for autism assessment, focusing on motor, learning, and attention/activity level domains. We aimed to determine what proportion of children in a cohort referred for an autism assessment showed traits of additional neurodivergences, and what proportion were further investigated.

Methods

We evaluated anonymised medical records of children aged between two and 17 years referred for autism assessment. We used validated questionnaires to assess for neurodivergent traits. A weighted scoring system was developed to determine traits in each neurodevelopmental domain and a score above the median was considered to indicate a neurodivergent trait. Evidence of further investigations were recorded. We then examined the relationships between autism traits and traits of additional neurodivergence.

Results

114 participants were included for evaluation. 62.3% (n = 71) had completed questionnaires for analysis. Of these, 71.8% (n = 51) scored greater than the median for at least one additional neurotype, indicating the presence of other neurodivergent traits, and 88.7% (n = 64) attracted a diagnosis of autism. Only 26.3% of children with evidence of additional neurotypes were further investigated beyond their autism assessment.

Conclusions

Our results demonstrate the extensive overlap between additional neurodivergent traits in a population of children referred with suspected autism and show that only a small proportion were further investigated. The use of standardised questionnaires to uncover additional neurodivergences may have utility in improving the holistic nature of neurodevelopmental assessments.

Cytomegalovirus detection is associated with ICU admission in non-AIDS and AIDS patients with <i>Pneumocystis jirovecii</i> pneumonia

by Alexandre Perret, Marion Le Marechal, Raphaele Germi, Daniele Maubon, Cécile Garnaud, Johan Noble, Aude Boignard, Loïc Falque, Mathieu Meunier, Théophile Gerster, Olivier Epaulard

Objectives

Cytomegalovirus (CMV) is frequently detected in lung and/or blood samples of patients with Pneumocystis jirovecii pneumonia (PJP), although this co-detection is not precisely understood. We aimed to determine whether PJP was more severe in case of CMV detection.

Methods

We retrospectively included all patients with a diagnosis of PJP between 2009 and 2020 in our centre and with a measure of CMV viral load in blood and/or bronchoalveolar lavage (BAL). PJP severity was assessed by the requirement for intensive care unit (ICU) admission.

Results

The median age of the 249 patients was 63 [IQR: 53–73] years. The main conditions were haematological malignancies (44.2%), solid organ transplantations (16.5%), and solid organ cancers (8.8%). Overall, 36.5% patients were admitted to ICU. CMV was detected in BAL in 57/227 patients; the 37 patients with viral load ≥3 log copies/mL were more frequently admitted to ICU (78.4% vs 28.4%, p Conclusions

PJP is more severe in the case of concomitant CMV detection. This may reflect either the deleterious role of CMV itself, which may require antiviral therapy, or the fact that patients with CMV reactivation are even more immunocompromised.

Reallocating time between device-measured 24-hour activities and cardiovascular risk in Asian American immigrant women: An isotemporal substitution model

by Chorong Park, Britta Larsen, Simona C. Kwon, Yuhe Xia, Marianna LaNoue, Victoria V. Dickson, Harmony R. Reynolds, Tanya M. Spruill

The 24-hour day consists of physical activity (PA), sedentary behavior, and sleep, and changing the time spent on one activity affects the others. Little is known about the impact of such changes on cardiovascular risk, particularly in Asian American immigrant (AAI) women, who not only have a higher cardiovascular risk but also place greater cultural value on family and domestic responsibilities compared to other racial/ethnic groups. The purpose of this study was to evaluate the effects of reallocating 30 minutes of each 24-hour activity component for another on BMI, waist circumference, and blood pressure in AAI women. Seventy-five AAI women completed 7 days of hip and wrist actigraphy monitoring and were included in the analysis (age = 61.5±8.0 years, BMI = 25.5±3.6 kg/m², waist circumference = 85.9±10.2 cm). Sleep was identified from wrist actigraphy data, and moderate-to-vigorous PA (MVPA), light PA, and sedentary behavior identified from hip actigraphy data. On average, the women spent 0.5 hours in MVPA, 6.2 hours in light PA, 10 hours in sedentary activities, and 5.3 hours sleeping within a 24-hour day. According to the isotemporal substitution models, replacing 30 minutes of sedentary behavior with MVPA reduced BMI by 1.4 kg/m² and waist circumference by 4.0 cm. Replacing that same sedentary time with sleep reduced BMI by 0.5 kg/m² and waist circumference by 1.4 cm. Replacing 30 minutes of light PA with MVPA decreased BMI by 1.6 kg/m² and waist circumference by 4.3 cm. Replacing 30 minutes of light PA with sleep also reduced BMI by 0.8 kg/m² and waist circumference by 1.7 cm. However, none of the behavioral substitutions affected blood pressure. Considering AAI women’s short sleep duration, replacing their sedentary time with sleep might be a feasible strategy to reduce their BMI and waist circumference.

Factors associated with an increased risk of developing pneumonia during acute ischemic stroke hospitalization

by Pornpong Jitpratoom, Adhiratha Boonyasiri

Stroke-associated pneumonia (SAP) is a common complication of acute ischemic stroke (AIS). This single-center retrospective observational study aimed to identify factors associated with SAP and predictors of poor outcomes in hospitalized patients with AIS. The study included patients admitted to Chumphon Khet Udomsakdi Hospital in Thailand within 7 days of the onset of AIS between July 2019 and July 2020. The patients were divided according to whether they were diagnosed with SAP during hospitalization into a pneumonia group and a non-pneumonia (control) group. Factors associated with SAP were identified. After 3 months, the patients with AIS were divided into those with a poor outcome (modified Rankin scale [mRS] score ≥4) and those with a non-poor outcome (mRS score

Cross-sectional study of attitudes toward online continuing dental education in Libya during the COVID-19 pandemic

by Ranya F. Elemam, Jamal M. El Swiah, Abduallah O. Durda, Nagwa N. Hegazy

During the COVID-19 pandemic, many educational institutions switched to e-learning educational platforms. This approach was essential but raised challenges, particularly in training practitioners for medical emergencies. This approach not only led to global challenges and a need for rapid adaptation, but also raised inequities across countries, with some facing far more technical challenges than others. In Libya, low investment in education technology and unpredictable internet connectivity limited its integration into schools and universities even before the pandemic. The current study reports feedback from an online continuing dental education (CDE) course for dental practitioners that was developed emergently during the pandemic and aimed to address the challenges posed by Libya’s internet environment. Participants were recruited through social media and received an 8-hour online CDE course consisting of three modules. Participants were invited to complete a pre-course demographic/informational survey on a Google form. After passing all modules, students were prompted to complete a post-course survey consisting of 23, five-point Likert scale questions. Respondents included 43 females (74.1%) and 15 males (25.9%). For ~50% of the cohort (n = 32), this was their first online clinical course. 87.9% of post-course participants rated the course as a positive learning experience, while 90.9% agreed their learning outcomes had been achieved. Most participants (97%) agreed the course instructor explained all concepts clearly. In total, 81.8% agreed that the technology effectively supported their learning. Most agreed that a clear demarcation between each course module existed and that the language and depth of the material were adequate. Some students reported technical difficulties, and 33.3% saw repetitions in the modules. However, all post-course respondents said they would recommend the online course to colleagues. Libyan dental practitioners showed high satisfaction levels towards the e-learning process, course content, instructors’ attitudes, and overall e-learning experience despite the inherent e-learning challenges posed in this country.

Understanding volunteerism among dental students and professionals to reach Saudi Arabia Vision 2030 goals

by Khalid Aboalshamat, Turki Alayyafi, Ghassan Elaiwa, Mishal Assayegh, Abdulmalk Alqaidi

Background

Volunteering can be defined as activities a person does for free to help another person or group. Saudi Vision 2030 has a target of one million volunteers from the country by 2030. The aim of this study was to find out the frequencies of the motives, barriers, and experiences of volunteering dental students and dentists in Saudi Arabia.

Materials and methods

In this cross-sectional study, 655 dental students and dentists from 37 cities around Saudi Arabia answered a questionnaire of 59 questions derived from previous studies. The questionnaire was distributed through social media. SPSS software was used to analyze the data, with p-value of 0.05 as significant. Chi-square was used for analytical statistics.

Results

The chance to learn in a health-related field (84.58%) was the most motivating factor to volunteer, and the least motivating factor was financial compensation (46.72%). Females had multiple significantly higher motives percentages than males (p Conclusions

A high percentage of dental students and dentists in Saudi Arabia engage in volunteer activities. Nevertheless, various impediments must be addressed to achieved the targeted key performance indicator of Saudi Arabia Vision 2030.

Protective and risk factors of mental health of working age adults with adventitious total bilateral blindness and low vision: A scoping review protocol

by Nneoma Dike, Lucia D’Ambruoso, Heather May Morgan, Zoë Skea, Emma-Louise Tarburn

Vision loss has been associated with mental health problems such as depression, anxiety, and post-traumatic stress disorder, which significantly impact lives of working age adults with adventitious total bilateral blindness and low vision. It is imperative, therefore, to prioritize the mental health in this population by exploring and understanding the factors that impact on their mental health. Hence, the objective of this scoping review is to identify and chart existing literature on the protective and risk factors of mental health of working age adults with adventitious total bilateral blindness and low vision. We developed this scoping review protocol in line with the Joanna Briggs Institute guidance. This scoping review will include publications in English language with no date restrictions exploring the protective and risk factors of mental health of our study population. A three-step search strategy will be employed. Searches will be carried out in the following databases: Medline, Embase, PsycInfo, PsycArticles, CINAHL and Web of Science. Search for grey literature will be conducted in Google, Google Scholar and Websites dedicated to information on visual impairment. Collated results will be imported into Endnote Basic (Clarivate) for deduplication. Two reviewers will independently conduct double screening of all the titles and abstracts in Rayyan- a web application, and full texts in Endnote while three other reviewers will conduct screening of a subset of for example 10% of titles and abstracts and full texts. Furthermore, two reviewers will independently conduct double data extraction while three other reviewers will revise, cross check, and correct any extraction errors. Extracted data will be presented in tabular formats and summarized descriptively in line with the research objectives. This scoping review will generate evidence on factors impacting the mental health of the working age adults with adventitious total bilateral blindness and low vision as well as critically highlight gaps in the literature. The findings will inform and critically underpin future empirical research which will explore the lived experiences of working age people with adventitious total bilateral blindness. Additionally, evidence from this review will inform the development of interventions in the promotion of mental health as well as assisting rehabilitation specialists and workers, public health practitioners and other relevant stakeholders in addressing the mental health needs of working age adults with adventitious total bilateral blindness and low vision.

Ketogenic diet preserves muscle mass and strength in a mouse model of type 2 diabetes

by Sol Been Park, Soo Jin Yang

Diabetes is often associated with reduced muscle mass and function. The ketogenic diet (KD) may improve muscle mass and function via the induction of nutritional ketosis. To test whether the KD is able to preserve muscle mass and strength in a mouse model of type 2 diabetes (T2DM), C57BL/6J mice were assigned to lean control, diabetes control, and KD groups. The mice were fed a standard diet (10% kcal from fat) or a high-fat diet (HFD) (60% kcal from fat). The diabetic condition was induced by a single injection of streptozotocin (STZ; 100 mg/kg) and nicotinamide (NAM; 120 mg/kg) into HFD-fed mice. After 8-week HFD feeding, the KD (90% kcal from fat) was fed to the KD group for the following 6 weeks. After the 14-week experimental period, an oral glucose tolerance test and grip strength test were conducted. Type 2 diabetic condition induced by HFD feeding and STZ/NAM injection resulted in reduced muscle mass and grip strength, and smaller muscle fiber areas. The KD nutritional intervention improved these effects. Additionally, the KD altered the gene expression of nucleotide-binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome- and endoplasmic reticulum (ER) stress-related markers in the muscles of diabetic mice. Collectively, KD improved muscle mass and function with alterations in NLRP3 inflammasome and ER stress.

Efficacy of early cardiac rehabilitation after acute myocardial infarction: Randomized clinical trial protocol

by Caroline Schon, Amanda Felismino, Joceline de Sá, Renata Corte, Tatiana Ribeiro, Selma Bruno

The acute myocardial infarction (AMI) present high mortality rate that may be reduced with cardiac rehabilitation. Despite its good establishment in outpatient care, few studies analyzed cardiac rehabilitation during hospitalization. Thus, this study aims to clarify the safety and efficacy of early cardiac rehabilitation after AMI. This will be a clinical, controlled, randomized trial with blind outcome evaluation and a superiority hypothesis. Twenty-four patients with AMI will be divided into two groups (1:1 allocation ratio). The intervention group will receive an individualized exercise-based cardiac rehabilitation protocol during hospitalization and a semi-supervised protocol after hospital discharge; the control group will receive conventional care. The primary outcomes will be the cardiac remodeling assessed by cardiac magnetic resonance imaging, functional capacity assessed by maximal oxygen consumption, and cardiac autonomic balance examined via heart rate variability. Secondary outcomes will include safety and the total exercise dose provided during the protocol. Statistical analysis will consider the intent-to-treat analysis. Trial registration. Trial registration number: Brazilian Registry of Clinical Trials (ReBEC) (RBR- 9nyx8hb).

Individual and environmental variables related to outdoor walking among older adults: Verifying a model to guide the design of interventions targeting outdoor walking

by Yixiu Liu, Nancy M. Salbach, Sandra C. Webber, Ruth Barclay

Objective

To estimate the relationships between individual and environmental variables and outdoor walking (OW) in older adults with OW limitations through verifying a conceptual model.

Methods

Baseline data from 205 older adults participating in a randomized trial of a park-based OW program were analyzed using structural equation modeling. We evaluated a three latent factor model: OW (accelerometry and self-report); individual factors (balance; leg strength; walking self-confidence, speed and endurance; mental health; education; income; car access); and environmental factors (neighbourhood walkability components).

Results

Mean age was 75 years; 73% were women. Individual factors was significantly associated with OW (β = 0.39, p p Conclusions

Better walking capacity and more confidence in the ability to walk outdoors are associated with higher OW in older adults. Better neighbourhood walkability is indirectly associated with more OW. The conceptual model demonstrates an individual and environment association; if the capacity of the individual is increased (potentially through walking interventions), they may be able to better navigate environmental challenges.

Novel ensemble learning approach with SVM-imputed ADASYN features for enhanced cervical cancer prediction

by Raafat M. Munshi

Cervical cancer remains a leading cause of female mortality, particularly in developing regions, underscoring the critical need for early detection and intervention guided by skilled medical professionals. While Pap smear images serve as valuable diagnostic tools, many available datasets for automated cervical cancer detection contain missing data, posing challenges for machine learning models’ efficacy. To address these hurdles, this study presents an automated system adept at managing missing information using ADASYN characteristics, resulting in exceptional accuracy. The proposed methodology integrates a voting classifier model harnessing the predictive capacity of three distinct machine learning models. It further incorporates SVM Imputer and ADASYN up-sampled features to mitigate missing value concerns, while leveraging CNN-generated features to augment the model’s capabilities. Notably, this model achieves remarkable performance metrics, boasting a 99.99% accuracy, precision, recall, and F1 score. A comprehensive comparative analysis evaluates the proposed model against various machine learning algorithms across four scenarios: original dataset usage, SVM imputation, ADASYN feature utilization, and CNN-generated features. Results indicate the superior efficacy of the proposed model over existing state-of-the-art techniques. This research not only introduces a novel approach but also offers actionable suggestions for refining automated cervical cancer detection systems. Its impact extends to benefiting medical practitioners by enabling earlier detection and improved patient care. Furthermore, the study’s findings have substantial societal implications, potentially reducing the burden of cervical cancer through enhanced diagnostic accuracy and timely intervention.

Diagnostic contribution of multi-frequency vibrometry to detection of peripheral neuropathy in type 1 diabetes mellitus compared with nerve conduction studies

by Linnéa Ekman, Lars B. Dahlin, Gert S. Andersson, Eero Lindholm

Aim

The aim was to assess the use of multi-frequency vibrometry (MFV) in detecting diabetic peripheral neuropathy (DPN) in type 1 diabetes in comparison to nerve conduction studies (NCS) and neurothesiometer (NT). Our objectives were to examine how VPTs correlated with NCS parameters, evaluate the efficacy of MFV in distinguishing DPN as well as to investigate whether MFV procedure could be based on fewer frequencies.

Methods

Adults with type 1 diabetes with previous MFV examinations were recruited at Skåne University Hospital in Malmö, Sweden, between 2018 and 2020. Participants were examined regarding nerve function in the lower limbs through MFV, NT and NCS.

Results

A total of 66 participants (28 women and 38 men) with a median age of 50 (39 to 64) years were included in the study. Through NCS assessment, 33 participants (50%) were diagnosed with DPN. We found negative correlations between VPTs and all NCS parameters, where the strongest correlation was found between sural nerve amplitude and the 125 Hz frequency of MFV. A combination of four frequencies, two low (4 and 8 Hz) and two high (125 and 250 Hz), showed the highest classification efficacy (AUC 0.83, 95% CI 0.73–0.93).

Conclusion

We conclude that a strong correlation exists between the sural nerve amplitude and the VPTs at 125 Hz and that VPT testing with MFV can be focused on only four frequencies instead of seven, thus shortening test time, to distinguish DPN in the lower limb.

Evaluation of new strain (AAD16) of <i>Beauveria bassiana</i> recovered from Japanese rhinoceros beetle: Effects on three coleopteran insects

by Souvic Sarker, Hyong Woo Choi, Un Taek Lim

A strain (AAD16) of the entomopathogenic fungus Beauveria bassiana (Balsamo) Vuillemin was isolated from field-collected Japanese rhinoceros beetle, Allomyrina dichotoma (L.) (Coleoptera: Scarabaeidae). Its virulence was compared with another strain (ARP14) recovered from a cadaver of Riptortus pedestris (F.) (Hemiptera: Alydidae) focusing on its effect on three coleopteran, i.e., Tenebrio molitor L., A. dichotoma, and Monochamus alternatus Hope. The LT₅₀ value of T. molitor for two larval sizes, i.e., 16–18 and 22–24 mm, was 15.3 and 19.4% lower for strain AAD16 compared to strain ARP14, respectively. Furthermore, after 8 and 10 days of exposure, the mycosis rate of strain AAD16 was 1.3 and 1.2 times higher than that of strain ARP14 in the 16–18 and 22–24 mm larval sizes, respectively. The LT₅₀ for M. alternatus larvae was 23.2% lower on strain AAD16 than on strain ARP14. In addition, the LT₅₀ for M. alternatus adults was 47.1% lower for strain AAD16 compared to control. The mycosis rate of strain AAD16 on M. alternatus larvae was 1.8 higher than that of strain ARP14 after 120 hours of exposure. The strain AAD16 also showed higher larval mortality (90%) for A. dichotoma compared to strain ARP14 (45.0%) at 28 days after exposure. These results suggest that B. bassiana AAD16 can be a potential biological control agent against coleopteran pests.

Impact of exercise training associated with enalapril treatment on blood pressure variability and renal dysfunctions in an experimental model of arterial hypertension and postmenopause

by Michel Pablo dos Santos Ferreira Silva, Maycon Junior Ferreira, Tânia Plens Shecaira, Danielle da Silva Dias, Débora Conte Kimura, Maria Cláudia Irigoyen, Guiomar Nascimento Gomes, Kátia De Angelis

Objective

In this study, we aimed to investigate the effects of the concurrent exercise training (CET) associated with the enalapril maleate on blood pressure variability (BPV) and renal profile in an experimental model of arterial hypertension (AH) and postmenopause.

Methods

Female ovariectomized spontaneously hypertensive rats (SHR) were distributed into 4 groups (n = 8/group): sedentary (SO), sedentary + enalapril (SOE), trained (TO) and trained + enalapril (TOE). Both enalapril (3mg/kg) and CET (3 days/week) were conducted during 8 weeks. Blood pressure (BP) was directly recorded for BPV analyses. Renal function, morphology, inflammation and oxidative stress were assessed.

Results

The SOE, TO e TOE groups presented decreased systolic BP compared with SO. Both trained groups (TO and TOE) presented lower BPV and increased baroreflex sensitivity (TO: 0.76 ± 0.20 and TOE: 1.02 ± 0.40 vs. SO: 0.40 ± 0.07 ms/mmHg) compared with SO group, with additional improvements in TOE group. Creatinine and IL-6 levels were reduced in SOE, TO and TOE compared with SO group, while IL-10 was increased only in TOE group (vs. SO). Enalapril combined with CET promote reduction in lipoperoxidation (TOE: 1.37 ± 0.26 vs. SO: 2.08 ± 0.48 and SOE: 1.84 ± 0.35 μmol/mg protein) and hydrogen peroxide (TOE: 1.89 ± 0.40 vs. SO: 3.70 ± 0.19 and SOE: 2.73 ± 0.70 μM), as well as increase in catalase activity (vs. sedentary groups). The tubulointerstitial injury was lower in interventions groups (SOE, TO and TOE vs. SO), with potentialized benefits in the trained groups.

Conclusions

Enalapril combined with CET attenuated BPV and baroreflex dysfunctions, probably impacting on end-organ damage, as demonstrated by attenuation in the AH-induced renal inflammations, oxidative stress and morphofunctional impairments in postmenopausal rats.

Dietary quality and cardiometabolic indicators in the USA: A comparison of the Planetary Health Diet Index, Healthy Eating Index-2015, and Dietary Approaches to Stop Hypertension

by Sarah M. Frank, Lindsay M. Jaacks, Christy L. Avery, Linda S. Adair, Katie Meyer, Donald Rose, Lindsey Smith Taillie

Background

The Planetary Health Diet Index (PHDI) measures adherence to the sustainable dietary guidance proposed by the EAT-Lancet Commission on Food, Planet, Health. To justify incorporating sustainable dietary guidance such as the PHDI in the US, the index needs to be compared to health-focused dietary recommendations already in use. The objectives of this study were to compare the how the Planetary Health Diet Index (PHDI), the Healthy Eating Index-2015 (HEI-2015) and Dietary Approaches to Stop Hypertension (DASH) relate to cardiometabolic risk factors.

Methods and findings

Participants from the National Health and Nutrition Examination Survey (2015–2018) were assigned a score for each dietary index. We examined disparities in dietary quality for each index. We used linear and logistic regression to assess the association of standardized dietary index values with waist circumference, blood pressure, HDL-C, fasting plasma glucose (FPG) and triglycerides (TG). We also dichotomized the cardiometabolic indicators using the cutoffs for the Metabolic Syndrome and used logistic regression to assess the relationship of the standardized dietary index values with binary cardiometabolic risk factors. We observed diet quality disparities for populations that were Black, Hispanic, low-income, and low-education. Higher diet quality was associated with improved continuous and binary cardiometabolic risk factors, although higher PHDI was not associated with high FPG and was the only index associated with lower TG. These patterns remained consistent in sensitivity analyses.

Conclusions

Sustainability-focused dietary recommendations such as the PHDI have similar cross-sectional associations with cardiometabolic risk as HEI-2015 or DASH. Health-focused dietary guidelines such as the forthcoming 2025–2030 Dietary Guidelines for Americans can consider the environmental impact of diet and still promote cardiometabolic health.

Optimizing CO₂ field flooding during sternotomy: In vitro confirmation of the Karolinska studies

by Mira Puthettu, Stijn Vandenberghe, Spyros Balafas, Clelia Di Serio, Geni Singjeli, Alberto Pagnamenta, Stefanos Demertzis

Although CO₂ field-flooding was first used during cardiac surgery more than 60 years ago, its efficacy is still disputed. The invisible nature of the gas and the difficulty in determining the “safe” quantity to protect the patient are two of the main obstacles to overcome for its validation. Moreover, CO₂ concentration in the chest cavity is highly sensitive to procedural aspects, such suction and hand movements. Based on our review of the existing literature, we identified four major factors that influence the intra-cavity CO₂ concentration during open-heart surgery: type of delivery device (diffuser), delivery CO₂ flow rate, diffuser position around the wound cavity, and its orientation inside the cavity. In this initial study, only steady state conditions were considered to establish a basic understanding on the effect of the four above-mentioned factors. Transient factors, such as suction or hand movements, will be reported separately.

PIK3CA regulates development of diabetes retinopathy through the PI3K/Akt/mTOR pathway

by Ruijuan Guan, Zefeng Kang, Ling Li, Xin Yan, Tianpeng Gao

Objective

To explore their association with the development of diabetes retinopathy (DR), single nucleotide polymorphism (SNP) mutations were screened out by high-throughput sequencing and validated in patients diagnosed with DR. To understand the role of PIK3CA in the pathogenesis of DR and explore the relationship between PIK3CA,phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR),and DR, the effect of PIK3CA.rs17849079 mutation was investigated in a DR cell model.

Methods

Twelve patients diagnosed with DR at the Qinghai Provincial People’s Hospital from September 2020 to June 2021 were randomly selected as the case group, while 12 healthy subjects of similar age and gender who underwent physical examination in Qinghai Provincial People’s Hospital physical examination center during the same period were randomly selected as the control group. Blood samples (2 mL) were collected from both groups using EDTA anticoagulant blood collection vessels and frozen at −20°C for future analysis. SNP mutations were detected by high-throughput sequencing, and the shortlisted candidates were subjected by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The detected SNP candidates were verified by expanding the sample size (first validation: 56 patients in the case group and 58 controls; second validation: 157 patients in the case group and 96 controls). A lentivirus vector carrying mutated or wild-type PIK3CA.rs17849079 was constructed. ARPE-19 cells were cultured in a medium supplemented with 10% fetal bovine serum (FBS) to establish a DR cell model. PIRES2-PIK3CA-MT and PIRES2-PIK3CA-WT vectors were transfected into DR model cells, which were categorized into control, mannitol, model, empty vector, PIK3CA wild-type, and PIK3CA mutant-type groups. Cell activity was detected by the cell counting kit (CCK)-8 assay, and cellular apoptosis was evaluated by flow cytometry. Glucose concentration and levels of cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-1β were detected using enzyme-linked immunosorbent assay kits. The expression of PIK3CA, AKT1, mTOR, and VEGF genes was detected by real-time quantitative polymerase chain reaction (RT-qPCR), while the expression of PI3K, p-PI3K, AKT1, p-AKT1, mTOR, p-mTOR, and VEGF proteins was detected by western blotting.

Results

The mutated SNPs were mainly enriched in the PI3K/AKT pathway, calcium ion pathway, and glutamatergic synaptic and cholinergic synaptic signaling pathways. Seven SNPs, including PRKCE.rs1533476, DNAH11.rs10485983, ERAP1.rs149481, KLHL1.rs1318761, APOBEC3C.rs1969643, FYN.rs11963612, and KCTD1.rs7240205, were not related to the development of DR. PIK3CA.rs17849079 was prone to C/T mutation. The risk of DR increased with the presence of the C allele and decreased in the presence of the T allele. High glucose induced the expression of PIK3CA and VEGF mRNAs as well as the expression of PI3K, p-PI3K, p-AKT1, p-mTOR, and VEGF proteins in ARPE-19 cells, which led to secretion of inflammatory factors TNF-αand IL-1, cell apoptosis, and inhibition of cell proliferation. The PIK3CA.rs17849079 C allele accelerated the progression of DR. These biological effects were inhibited when the C allele of PIK3CA.rs17849079 was mutated to T allele.

Conclusion

The mutated SNP sites in patients with DR were mainly enriched in PI3K/AKT, calcium ion, and glutamatergic synaptic and cholinergic synaptic signaling pathways. The rs17849079 allele of PIK3CA is prone to C/T mutation where the C allele increases the risk of DR. High glucose activates the expression of PIK3CA and promotes the phosphorylation of PI3K, which leads to the phosphorylation of AKT and mTOR. These effects consequently increase VEGF expression and accelerate the development of DR. The C to T allele mutation in PIK3CA.rs17849079 can play a protective role and reduce the risk of DR.

Challenges with pediatric antiretroviral therapy administration: Qualitative perspectives from caregivers and HIV providers in Kenya

by Michala Sliefert, May Maloba, Catherine Wexler, Frederick Were, Yvonne Mbithi, George Mugendi, Edward Maliski, Zachary Nicolay, Gregory Thomas, Shadrack Kale, Nicodemus Maosa, Sarah Finocchario-Kessler

Background

Current formulations of pediatric antiretroviral therapy (ART) for children with HIV present significant barriers to adherence, leading to drug resistance, ART ineffectiveness, and preventable child morbidity and mortality. Understanding these challenges and how they contribute to suboptimal adherence is an important step in improving outcomes. This qualitative study describes how regimen-related challenges create barriers to adherence and impact families.

Methods

We conducted key informant interviews (KIIs) with 30 healthcare providers and 9 focus group discussions (FGDs) with a total of 72 caregivers, across three public hospitals in Siaya and Mombasa Kenya. The KIIs and FGDs were audio recorded, translated, and transcribed verbatim. The transcripts were hand coded based on emergent and a-priori themes.

Results

Caregivers discussed major regimen-related challenges to adherence included poor palatability of current formulations, complex preparation, and administration (including measuring, crushing, dissolving, mixing), complex drug storage, and frequent refill appointments and how these regimen-related challenges contributed to individual and intrapersonal barriers to adherence. Caregivers discussed how poor taste led to child anxiety, refusal of medications, and the need for caregivers to use bribes or threats during administration. Complex preparation led to concerns and challenges about maintaining privacy and confidentiality, especially during times of travel. Providers corroborated this patient experience and described how these challenges with administration led to poor infant outcomes, including high viral load and preventable morbidity. Providers discussed how the frequency of refills could range from every 2 weeks to every 3 months, depending on the patient. Caregivers discussed how these refill frequencies interrupted work and school schedules, risked unwanted disclosure to peers, required use of financial resources for travel, and ultimately were a challenge to adherence.

Conclusion

These findings highlight the need for improved formulations for pediatric ART to ease the daily burden on caregivers and children to increase adherence, improve child health, and overall quality of life of families.

An investigation of the modulatory effects of empathic and autistic traits on emotional and facial motor responses during live social interactions

by Chun-Ting Hsu, Wataru Sato, Sakiko Yoshikawa

A close relationship between emotional contagion and spontaneous facial mimicry has been theoretically proposed and is supported by empirical data. Facial expressions are essential in terms of both emotional and motor synchrony. Previous studies have demonstrated that trait emotional empathy enhanced spontaneous facial mimicry, but the relationship between autistic traits and spontaneous mimicry remained controversial. Moreover, previous studies presented faces that were static or videotaped, which may lack the “liveliness” of real-life social interactions. We addressed this limitation by using an image relay system to present live performances and pre-recorded videos of smiling or frowning dynamic facial expressions to 94 healthy female participants. We assessed their subjective experiential valence and arousal ratings to infer the amplitude of emotional contagion. We measured the electromyographic activities of the zygomaticus major and corrugator supercilii muscles to estimate spontaneous facial mimicry. Individual differences measures included trait emotional empathy (empathic concern) and the autism-spectrum quotient. We did not find that live performances enhanced the modulatory effect of trait differences on emotional contagion or spontaneous facial mimicry. However, we found that a high trait empathic concern was associated with stronger emotional contagion and corrugator mimicry. We found no two-way interaction between the autism spectrum quotient and emotional condition, suggesting that autistic traits did not modulate emotional contagion or spontaneous facial mimicry. Our findings imply that previous findings regarding the relationship between emotional empathy and emotional contagion/spontaneous facial mimicry using videos and photos could be generalized to real-life interactions.

The Fit After Baby randomized controlled trial: An mHealth postpartum lifestyle intervention for women with elevated cardiometabolic risk

by Jacinda M. Nicklas, Laura Pyle, Andrey Soares, Jennifer A. Leiferman, Sheana S. Bull, Suhong Tong, Ann E. Caldwell, Nanette Santoro, Linda A. Barbour

Background

Postpartum women with overweight/obesity and a history of adverse pregnancy outcomes are at elevated risk for cardiometabolic disease. Postpartum weight loss and lifestyle changes can decrease these risks, yet traditional face-to-face interventions often fail. We adapted the Diabetes Prevention Program into a theory-based mobile health (mHealth) program called Fit After Baby (FAB) and tested FAB in a randomized controlled trial.

Methods

The FAB program provided 12 weeks of daily evidence-based content, facilitated tracking of weight, diet, and activity, and included weekly coaching and gamification with points and rewards. We randomized women at 6 weeks postpartum 2:1 to FAB or to the publicly available Text4baby (T4B) app (active control). We measured weight and administered behavioral questionnaires at 6 weeks, and 6 and 12 months postpartum, and collected app user data.

Results

81 eligible women participated (77% White, 2% Asian, 15% Black, with 23% Hispanic), mean baseline BMI 32±5 kg/m² and age 31±5 years. FAB participants logged into the app a median of 51/84 (IQR 25,71) days, wore activity trackers 66/84 (IQR 43,84) days, logged weight 17 times (IQR 11,24), and did coach check-ins 5.5/12 (IQR 4,9) weeks. The COVID-19 pandemic interrupted data collection for the primary 12-month endpoint, and impacted diet, physical activity, and body weight for many participants. At 12 months postpartum women in the FAB group lost 2.8 kg [95% CI -4.2,-1.4] from baseline compared to a loss of 1.8 kg [95% CI -3.8,+0.3] in the T4B group (p = 0.42 for the difference between groups). In 60 women who reached 12 months postpartum before the onset of the COVID-19 pandemic, women randomized to FAB lost 4.3 kg [95% CI -6.0,-2.6] compared to loss in the control group of 1.3 kg [95% CI -3.7,+1.1] (p = 0.0451 for the difference between groups).

Conclusions

There were no significant differences between groups for postpartum weight loss for the entire study population. Among those unaffected by the COVID pandemic, women randomized to the FAB program lost significantly more weight than those randomized to the T4B program. The mHealth FAB program demonstrated a substantial level of engagement. Given the scalability and potential public health impact of the FAB program, the efficacy for decreasing cardiometabolic risk by increasing postpartum weight loss should be tested in a larger trial.