Standardized Research Protocol Research Articles

Do Parental Hormone Levels Synchronize During the Prenatal and Postpartum Periods? A Systematic Review.

Physiological synchrony is the phenomenon of linked physiological processes among two or more individuals. Evidence of linkage between dyads has been found among a broad range of physiological indices, including the endocrine systems. During the transition to parenthood, both men and women undergo hormonal changes that facilitate parenting behavior. The present review sought to address the question as to whether hormonal synchronization occurs among expecting or new parents. A systematic literature search yielded 13 eligible records. The evidence of cortisol synchrony during the prenatal period, with additional testosterone, prolactin, and progesterone covariations in the time leading up to childbirth, was found to be most significant. During the postpartum period, parental synchrony was reported for oxytocin, testosterone, and cortisol levels. The implications of these covariations were found to translate into adaptive parenting behaviors and the facilitation of romantic bond. Associations with infant development were also reported, suggesting far-reaching effects of hormonal synchrony outside the parental dyad. The results highlight the importance of physiological interrelatedness during this sensitive period, underscoring the need for further research in this field. In view of the limited data available in this research domain, we have put forward a framework for future studies, recommending the adoption of standardized research protocols and repeated collections of specimens.

Epithelial Cell Infection Analyses with Shigella.

The human-adapted enteric bacterial pathogen Shigella causes millions of infections each year, creates long-term growth effects among pediatric patients, and is a leading cause of diarrheal deaths worldwide. Infection induces watery or bloody diarrhea as a result of the pathogen transiting the gastrointestinal tract and infecting the epithelial cells lining the colon. With staggering increases in antibiotic resistance and the current lack of approved vaccines, standardized research protocols are critical to studying this formidable pathogen. Here, methodologies are presented to examine the molecular pathogenesis of Shigella using in vitro analyses of bacterial adherence, invasion, and intracellular replication in colonic epithelial cells. Prior to infection analyses, the virulence phenotype of Shigella colonies was verified by the uptake of the Congo red dye on agar plates. Supplemented laboratory media can also be considered during bacterial culturing to mimic in vivo conditions. Bacterial cells are then used in a standardized protocol to infect colonic epithelial cells in tissue culture plates at an established multiplicity of infection with adaptations to analyze each stage of infection. For adherence assays, Shigella cells are incubated with reduced media levels to promote bacterial contact with epithelial cells. For both invasion and intracellular replication assays, gentamicin is applied for various time intervals to eliminate extracellular bacteria and enable assessment of invasion and/or the quantification of intracellular replication rates. All infection protocols enumerate adherent, invaded, and/or intracellular bacteria by serially diluting infected epithelial cell lysates and plating bacterial colony forming units relative to infecting titers on Congo red agar plates. Together, these protocols enable independent characterization and comparisons for each stage of Shigella infection of epithelial cells to study this pathogen successfully.

An analysis of visual functioning and cerebral visual impairments in children with profound intellectual and multiple disabilities

The aim of this study was to gain insight into the visual functioning of children with profound intellectuual and multiple disabilities (PIMD). A mixed methods study was performed, determining cross-sectional quantitative ophthalmological/orthoptic data, and qualitative observational data with a standardized research protocol (SRP) of 73 children with PIMD. Descriptive statistics and correlations were used for analyses of the data. Using ophthalmological data, 90.4% of the participants were found visually impaired. Based on the visual acuity (VA) testing, 49.6% of the participants had an impaired VA (<0.3), and 15.3% could not be tested. Applying the SRP, profound cerebral visual impairment (CVI) was found in 43.8% of the participants; severe CVI in 28.8%; mild CVI in 13.7%; and no CVI in 12.3%. The correlation (Spearman’s rho) between CVI and severity of motor impairments was 0.61 ( p= .01). The results showed that visual impairment (VI) based on medical and ophthalmological data was present in nearly all of the participants with the highest prevalence among those with severe motor impairments. Providing specific information about visual functioning and the characteristics of CVI, using the SRP, may contribute to the individually adapted support of the development and partcipation of children with PIMD.

Editorial

The 36th Edition of GIRI was carried out under the theme: “GROUNDBREAKING SCIENCE: HOMEOPATHY AND THE FUTURE OF GLOBAL HEALTH” and provided a single opportunity for the participants to exchange scientific experiences, discuss new and standard research protocols, make new friendships, and gather the most important researchers involved with basic and/or clinical homeopathic research worldwide. The multidisciplinary feature of the GIRI meetings fits the concept of global health, since homeopathy favors the interconnection among people, animals, plants, and their environment, promoting its sustainable use in agriculture. The meeting aimed to examine the growing body of evidence around homeopathy and consider its role in addressing many urgent concerns, such as infectious diseases and antimicrobial resistance, aging populations, multimorbidity, polypharmacy, sustainability, and environmental factors, with special focus on the emerging evidence that homeopathic products may help mitigate the impact of climate change on agriculture – making plants and animals more bio-resilient – while also reducing the need for agricultural chemicals known to cause environmental harm.

Research progress on plant-derived exosome-like nanoparticles and their applications

Plant-derived exosome-like nanoparticles(PELNs) are a class of membranous vesicles with diameters approximately ranging from 30 to 300 nm, isolated from plant tissues. They contain components such as proteins, lipids, and nucleic acids. PELNs play an important role in the metabolism of plant substances and immune defense, and can also cross-regulate the physiological activities of fungi and animal cells, showing significant potential applications. In recent years, research on PELNs has significantly increased, highlighting three main issues:(1) the mixed sources of plant materials for PELNs;(2) the lack of a unified system for isolating and characterizing PELNs;(3) the urgent need to elucidate the molecular mechanisms underlying the cross-regulation of biological functions by PELNs. This article focused on these concerns. It began by summarizing the biological origin and composition of PELNs, discussing the techniques for isolating and characterizing PELNs, and analyzing their biomedical applications and potential future research directions., aiming to promote the establishment of standardized research protocols for PELNs and provide theoretical references for in-depth exploration of the mechanisms underlying PELNs' cross-regulatory effects.

A Drone Study of Sociality in the Finless Porpoise Neophocaena asiaeorientalis in the Ariake Sound, Japan

The social structure of animal populations is a fundamental component of their biology, influencing gene flow, habitat use, competition and co-operation around resources, and communication. However, ecological and social relationships can be challenging to describe in most marine mammals, who spend the majority of their lives underwater. The finless porpoise (Neophocaena asiaeorientalis) is one such cetacean species with a largely unknown social structure. Recent advances in drone technology enable more systematic surveys, photogrammetry, and photo-identification for diverse animal species. The present study aimed to validate new survey methods and provide a preliminary description of the spatiotemporal distribution of free-ranging finless porpoises in the coastal open-sea area of Ariake Sound, Japan. A vertical take-off and landing (VTOL) drone equipped with an action camera yielded GPS location datasets through line and area surveys, covering a total sea area of 120 km2. The results suggest highly flexible and varied aggregation sizes in finless porpoises. Distance analysis across individuals and aggregations revealed a cohesive tendency among groups, compared to solitaries and in pairs. Therefore, the present VTOL drone surveys both elucidated some social aspects of the study population and confirmed the efficacy of these standardized research protocols involving automated, programmed, and repeatable flight missions.

Determining the Impact of the COVID-19 Pandemic on Availability, Use, and Readiness of Family Planning and Contraceptive Services at Selected Primary Health Care Facilities in Africa and Asia: Protocol for a Mixed Methods Study.

The COVID-19 pandemic and the associated social restrictions may have disrupted the provision of essential services, including family planning (FP) and contraceptive services. This protocol is adapted from a generic study protocol titled "Health systems analysis and evaluations of the barriers to availability and readiness of sexual and reproductive health services in COVID-19 affected areas," conducted by the World Health Organization (WHO) Department of Reproductive Health and Research. This study aims to assess the availability and use of FP and contraceptive services in primary health facilities during and after the COVID-19 pandemic; assess the risk perceptions of COVID-19 stigma, barriers to access, and quality of services from clients' and providers' perspectives in the COVID-19-affected areas; and assess the postpandemic recovery of the facilities in the provision of FP and contraceptive services. In-depth interviews will be conducted with clients-women in the reproductive age group and their male partners who visit the selected health facilities for FP and contraceptive services-and health providers (the most knowledgeable person on FP and contraceptive service provision) at the selected health facilities. Focus group discussions will be conducted with clients at the selected health facilities and in the community. The in-depth interviews and focus group discussions will help to understand clients' and health service providers' perspectives of FP and contraceptive service availability and readiness in COVID-19-affected areas. A cross-sectional health facility assessment will be conducted in all the selected health facilities to determine the health facility infrastructure's ability and readiness to provide FP and contraceptive services and to capture the trends in FP and contraceptive services available during the COVID-19 pandemic. Scientific approval for this study is obtained from the WHO Research Project Review Panel, and the WHO Ethics Review Committee has given ethical approval in the 3 countries. Using a standardized research protocol will ensure that the results from this study can be compared across regions and countries. The study was funded in March 2021. It received ethics approval from the WHO Ethics Review Committee in February 2022. We completed data collection in September 2022. We plan to complete the data analysis by March 2023. We plan to publish the study results by Summer 2023. The findings from this study will provide a better understanding of the impact of the COVID-19 pandemic on FP and contraceptive services at the facility level, which will help policy makers and health managers develop and strengthen FP policies and services in health facilities to be more responsive to community needs. DERR1-10.2196/43329.

School-based Psychosocial interventions on mental health among Chinese rural children with traumatic experiences: a protocol using cluster randomized controlled trial

BackgroundThe first aim of this study is to test the effectiveness of school-based psychosocial interventions for improving mental health in rural Chinese children with traumatic experiences. The second aim is to examine which individual, family and school related factors could explain the effectiveness of school-based psychosocial interventions. Third, we will investigate whether individual, family, and school related conditions play a moderator role on the effectiveness of school-based psychosocial interventions.MethodsThis study will conduct a cluster randomized controlled trial (RCT) in a large sample of Chinese rural children. Four rural counties in Shandong (Central China), Henan (Central China), Inner Mongolia (Northern China), and Xinjiang (Western China) will be selected as study settings from which schools will be sampled. Each sampled school will be randomly allocated either the intervention groups or a control group. Randomization will be performed by the research member who is not involved in the intervention stage. In each school students in grade 5 or higher will be recruited to ensure that approximately 50 children aged 10 to 18 years will be included. In each county, one high school, one middle school, and one primary school will be randomly chosen as the intervention group, and the other three similar schools will be chosen as control (waiting list) groups. A standardized and uniform research protocol will be applied in all intervention schools. All school social workers and psychological teachers would receive one week of in-person training following procedures. School-based psychosocial interventions included 14 group sessions for 14 consecutive weeks.DiscussionThis study would develop school-based mental health promotion policy recommendations to improve Chinese rural children’s mental health. This study can provide solid evidence for the promotion of school-based intervention in general.Trial registrationChiCTR2300069405, Registered on 15 March 2023.

EVALUATION OF OILSEED RADISH ( Raphanus sativus L. var. oleiformis Pers.) OIL AS A POTENTIAL COMPONENT OF BIOFUELS

The growing interest in alternative fuels based on plant oils has led to the search for new plant species. Given this, during 2015–2020, oil from 12 varieties of oilseed radish was studied using standard research protocols. The average content of the dominant fatty acids in the oils studied was: [cis-9] oleic (C 18:1) 33.95% (Cv = 14.2%), [cis-9,12] linoleic (C 18:2) 16.20% (Cv = 20.8%), [cis-13] erucic (C 22:1) 15.18% (Cv = 17.9%), [cis-9, 12, 15] α-linolenic (C 18:3) 13.33% (Cv = 18.5%) and palmitic (C 16:0) 5.42% (Cv = 18.5%), with a monounsaturated fatty acid content of 59.69% and a ratio of polyunsaturated/monounsaturated fatty acids of 0.508. The studied varieties were ranked in the order of increasing suitability as a component of biofuels: ‘Zhuravka’ < ‘Raiduha’ < ‘Lybid’ < ‘Olga’ < ‘Iveya’ < ‘Ramonta’ < ‘Alpha’ < ‘Tambovchanka’ < ‘Fakel’ < ‘Snizhana’ < ‘Sabina’ < ‘Nika’. The technological suitability of oil from the ‘Zhuravka’ variety was confirmed based on analysis of its physicochemical parameters when subjected to polymerization (at 280 °C) and oxypolymerization (at 120 and 150 °C). Under these conditions the basic parameters of the oil varied within the technological limits that determine its suitability for thermodynamic combustion processes in systems with controlled pressure and temperature.

A Porcine Sepsis Model With Numerical Scoring for Early Prediction of Severity.

IntroductionSepsis can lead to organ dysfunctions with disturbed oxygen dynamics and life-threatening consequences. Since the results of organ-protective treatments cannot always be transferred from laboratory models into human therapies, increasing the translational potential of preclinical settings is an important goal. Our aim was to develop a standardized research protocol, where the progression of sepsis-related events can be characterized reproducibly in model experiments within clinically-relevant time frames.MethodsPeritonitis was induced in anesthetized minipigs injected intraperitoneally with autofeces inoculum (n = 27) or with saline (sham operation; n = 9). The microbial colony-forming units (CFUs) in the inoculum were retrospectively determined. After awakening, clinically relevant supportive therapies were conducted. Nineteen inoculated animals developed sepsis without a fulminant reaction. Sixteen hours later, these animals were re-anesthetized for invasive monitoring. Blood samples were taken to detect plasma TNF-α, IL-10, big endothelin (bET), high mobility group box protein1 (HMGB1) levels and blood gases, and sublingual microcirculatory measurements were conducted. Hemodynamic, respiratory, coagulation, liver and kidney dysfunctions were detected to characterize the septic status with a pig-specific Sequential Organ Failure Assessment (pSOFA) score and its simplified version (respiratory, cardiovascular and renal failure) between 16 and 24 h of the experiments.ResultsDespite the standardized sepsis induction, the animals could be clustered into two distinct levels of severity: a sepsis (n = 10; median pSOFA score = 2) and a septic shock (n = 9; median pSOFA score = 8) subgroup at 18 h of the experiments, when the decreased systemic vascular resistance, increased DO2 and VO2, and markedly increased ExO2 demonstrated a compensated hyperdynamic state. Septic animals showed severity-dependent scores for organ failure with reduced microcirculation despite the adequate oxygen dynamics. Sepsis severity characterized later with pSOFA scores was in correlation with the germ count in the induction inoculum (r = 0.664) and CFUs in hemocultures (r = 0.876). Early changes in plasma levels of TNF-α, bET and HMGB1 were all related to the late-onset organ dysfunctions characterized by pSOFA scores.ConclusionsThis microbiologically-monitored, large animal model of intraabdominal sepsis is suitable for clinically-relevant investigations. The methodology combines the advantages of conscious and anesthetized studies, and mimics human sepsis and septic shock closely with the possibility of numerical quantification of host responses.

Research Hotspots and Trends in Music Therapy Intervention for Patients With Dementia: A Bibliometrics and Visual Analysis of Papers Published From 2010 to 2021

BackgroundAs a serious public health problem, dementia has placed a heavy burden on society and families. Evidence suggests that the use of music therapy as a non-pharmacological intervention has certain advantages with respect to reducing the behavioral and psychological symptoms of dementia (BPSD) and improving the cognition and mental status of dementia patients. However, research trends and hotspots regarding music therapy intervention for dementia analysis have not been systematically studied via bibliometric analysis.MethodsWe searched the Web of Science Core Collection (WoSCC) for texts published between January 1, 2010, and October 31, 2021, and visualized country, institution, journal, keyword co-occurrence, keyword emergence and keyword clustering.ResultsA total of 217 articles from the WoSCC database were analyzed. In this research field, the annual number of publications has generally shown a slowly increasing trend, and the United States has the most publications and the most frequent cooperation among countries. University College London (UCL) has the most extensive influence among research institutions. Among articles, those published in the JOURNAL OF ALZHEIMER'S DISEASE were the most numerous, with 20 such articles being published, accounting for 9.22% (20/217) of the total. Comprehensive analysis of five clusters via biclustering shows that the research hotspots in this field during the past 11 years have mainly focused on the autobiographical memory, cognitive function, mental state and BPSD of dementia patients.ConclusionThis study conducted a bibliometric and visual analysis of relevant studies concerning music therapy intervention for dementia patients. Psychological problems faced by dementia patients and the topics of quality of life, individualized music therapy, the mental state of caregivers and other related topics may be important research directions in the future. Therefore, the question of how to develop standardized research protocols and identify unified efficacy evaluation indicators should be a focus of and difficulty for future research.

Plasma biomarkers for Alzheimer\u2019s Disease in relation to neuropathology and cognitive change

Plasma biomarkers related to amyloid, tau, and neurodegeneration (ATN) show great promise for identifying these pathological features of Alzheimer’s Disease (AD) as shown by recent clinical studies and selected autopsy studies. We have evaluated ATN plasma biomarkers in a series of 312 well-characterized longitudinally followed research subjects with plasma available within 5 years or less before autopsy and examined these biomarkers in relation to a spectrum of AD and related pathologies. Plasma Aβ42, Aβ40, total Tau, P-tau181, P-tau231 and neurofilament light (NfL) were measured using Single molecule array (Simoa) assays. Neuropathological findings were assessed using standard research protocols. Comparing plasma biomarkers with pathology diagnoses and ratings, we found that P-tau181 (AUC = 0.856) and P-tau231 (AUC = 0.773) showed the strongest overall sensitivity and specificity for AD neuropathological change (ADNC). Plasma P-tau231 showed increases at earlier ADNC stages than other biomarkers. Plasma Aβ42/40 was decreased in relation to amyloid and AD pathology, with modest diagnostic accuracy (AUC = 0.601). NfL was increased in non-AD cases and in a subset of those with ADNC. Plasma biomarkers did not show changes in Lewy body disease (LBD), hippocampal sclerosis of aging (HS) or limbic-predominant age-related TDP-43 encephalopathy (LATE) unless ADNC was present. Higher levels of P-tau181, 231 and NfL predicted faster cognitive decline, as early as 10 years prior to autopsy, even among people with normal cognition or mild cognitive impairment. These results support plasma P-tau181 and 231 as diagnostic biomarkers related to ADNC that also can help to predict future cognitive decline, even in predementia stages. Although NfL was not consistently increased in plasma in AD and shows increases in several neurological disorders, it had utility to predict cognitive decline. Plasma Aβ42/40 as measured in this study was a relatively weak predictor of amyloid pathology, and different assay methods may be needed to improve on this. Additional plasma biomarkers are needed to detect the presence and impact of LBD and LATE pathology.

Predicting Individual Treatment Response to rTMS for Motor Recovery After Stroke: A Review and the CanStim Perspective.

BackgroundRehabilitation is critical for reducing stroke-related disability and improving quality-of-life post-stroke. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulation technique used as stand-alone or adjunct treatment to physiotherapy, may be of benefit for motor recovery in subgroups of stroke patients. The Canadian Platform for Trials in Non-Invasive Brain Stimulation (CanStim) seeks to advance the use of these techniques to improve post-stroke recovery through clinical trials and pre-clinical studies using standardized research protocols. Here, we review existing clinical trials for demographic, clinical, and neurobiological factors which may predict treatment response to identify knowledge gaps which need to be addressed before implementing these parameters for patient stratification in clinical trial protocols.ObjectiveTo provide a review of clinical rTMS trials of stroke recovery identifying factors associated with rTMS response in stroke patients with motor deficits and develop research perspectives for pre-clinical and clinical studies.MethodsA literature search was performed in PubMed, using the Boolean search terms stroke AND repetitive transcranial magnetic stimulation OR rTMS AND motor for studies investigating the use of rTMS for motor recovery in stroke patients at any recovery phase. A total of 1,676 articles were screened by two blinded raters, with 26 papers identified for inclusion in this review.ResultsMultiple possible factors associated with rTMS response were identified, including stroke location, cortical thickness, brain-derived neurotrophic factor (BDNF) genotype, initial stroke severity, and several imaging and clinical factors associated with a relatively preserved functional motor network of the ipsilesional hemisphere. Age, sex, and time post-stroke were generally not related to rTMS response. Factors associated with greater response were identified in studies of both excitatory ipsilesional and inhibitory contralesional rTMS. Heterogeneous study designs and contradictory data exemplify the need for greater protocol standardization and high-quality controlled trials.ConclusionClinical, brain structural and neurobiological factors have been identified as potential predictors for rTMS response in stroke patients with motor impairment. These factors can inform the design of future clinical trials, before being considered for optimization of individual rehabilitation therapy for stroke patients. Pre-clinical models for stroke recovery, specifically developed in a clinical context, may accelerate this process.

Machine learning and artificial intelligence in research and healthcare

Artificial intelligence (AI) is a broad term referring to the application of computational algorithms that can analyze large data sets to classify, predict, or gain useful conclusions. Under the umbrella of AI is machine learning (ML). ML is the process of building or learning statistical models using previously observed real world data to predict outcomes, or categorize observations based on ‘training’ provided by humans. These predictions are then applied to future data, all the while folding in the new data into its perpetually improving and calibrated statistical model. The future of AI and ML in healthcare research is exciting and expansive. AI and ML are becoming cornerstones in the medical and healthcare-research domains and are integral in our continued processing and capitalization of robust patient EMR data. Considerations for the use and application of ML in healthcare settings include assessing the quality of data inputs and decision-making that serve as the foundations of the ML model, ensuring the end-product is interpretable, transparent, and ethical concerns are considered throughout the development process. The current and future applications of ML include improving the quality and quantity of data collected from EMRs to improve registry data, utilizing these robust datasets to improve and standardized research protocols and outcomes, clinical decision-making applications, natural language processing and improving the fundamentals of value-based care, to name only a few.

Author Response: Prediction of Long-term Cognitive Function After Minor Stroke Using Functional Connectivity

We thank the authors for the comment about our study.1 We agree that dependent and independent factors can indicate the cognitive status in the chronic phase after stroke. Further studies about the prediction of long-term cognitive impairment after stroke could combine demographic, clinical, imaging, and biological variables to improve the precision of machine-learning approaches. However, in our study, we showed that education and white matter hyperintensity load—which can be a marker of hypertension and diabetes mellitus type II2—had no effect on the cognitive status at 6 months and 36 months after stroke. Moreover, the inclusion criteria and research protocol were established to limit the variability. Patients included in the study had minor strokes with limited functional and cognitive impairment. Standardized clinical, imaging, and cognitive examinations were performed to limit the variability in our population. Finally, we validated our results on an independent population with similar stroke characteristics and a standardized research protocol.

Randomized controlled trial of neurologic music therapy in Parkinson\u2019s disease: research rehabilitation protocols for mechanistic and clinical investigations

BackgroundPresently available medications and surgical treatments for Parkinson’s disease have limited effects on fine motor problems and often leave patients with significant fine motor disability. Standard of care occupational therapy (OT) yields low efficacy, potentially due to a lack of standard protocols. Neurologic music therapy (NMT) techniques, especially rhythmic auditory stimulation which relies on interaction between rhythm and movement, have shown to be effective in PD gait rehabilitation possibly through their reliance on neural pathways that are not affected by PD. Therapeutic instrumental music performance (TIMP) is one other NMT technique that holds promise but which mode of action and efficacy has not been investigated in PD yet.MethodsOne hundred PD participants will be randomly assigned to receive 15 sessions of either TIMP with rhythm or TIMP without rhythm, standard of care OT, or to be waitlisted (control) over 5 consecutive weeks. Brain oscillatory responses will be collected using magnetoencephalography during an auditory-motor task to understand the underlying mechanisms. The Grooved Pegboard, the UPDRS III finger tap, and the finger-thumb opposition will be assessed to investigate clinical changes related to fine motor function. This project will also serve to confirm or refute our pilot data findings suggesting NMT relies on compensatory brain networks utilized by the PD brain to bypass the dysfunctional basal ganglia.DiscussionThis study aims to use standardized TIMP and OT research protocols for investigating the neuronal pathways utilized by each intervention and possibly study their efficacy with respect to fine motor rehabilitation via a randomized control trial in the PD population.Trial registrationClinicalTrials.gov NCT03049033. Registered on September 29, 2020

Dietary free sugar and dental caries in children: A systematic review on longitudinal studies.

Background: Dental caries, as a multi-factorial problem, is prevalent among children. The aim of this review was to assess the association between dietary free sugars (DFS) consumption and dental caries in 6- to 12-year-old children in the recent longitudinal e vidence. Methods: In this systematic review, database search was performed in PubMed, Embase, ISI Web of Science and Scopus using the keywords "diet", "dental caries" and "school children".We considered the articles published in English from 2004 to 2019. After duplicate removal,title, abstract data basell text of all included papers were assessed by two independent reviewers. The quality of included papers was assessed using the Newcastle-Ottawa scale. Results: From 2122 papers, ten longitudinal studies were included. In the included studies, the consumption of 100% juice (daily), candy (more than once a week), and soft drink and sweet drinks (at bedtime) were highly associated with caries in children. In few studies, daily consumption of water and dairy products was reported to be protective. However, some studies reported non-significant association between consumption of different sugary items and dental caries. The quality of included studies was moderate. Heterogeneity was observed in the measurement of caries outcome, and data collection tool for diet assessment, and statistical measure, which impeded the meta-analysis of data. Conclusion: The methodology and results in the longitudinal studies on the association of dietary free sugar consumption and dental caries in schoolchildren were heterogeneous, which urge the need for further standard research protocols in this area.

The Relationship between Individual and Family Characteristics and Cyberbullying Exposure in a Nationally Representative Sample of School-Aged Children Living in Serbia

The study provides evidence on the individual and family factors as potential predictors (odds ratio—OR and 95% CI) of cyber-violence among school-aged children (11–17 years old) from 64 schools participating in the 2017 Serbian Study on health behavior in school-age children (HBSC). The standardized international HBSC research protocol was used. The study population was the nationally representative sample of 3267 students of V and VII grades of primary and I grade of secondary schools in Serbia. Potential predictors for the probability of occurrence vs. non-occurrence of cyberbullying exposure at least once and multiple times were identified among 24 explanatory variables, including the individual characteristics and family context. The cyberbullying exposure was more prevalent among girls than among boys of school-age, i.e., over one in seven girls and one in ten boys were exposed to cyberbullying. Over one in seven students at age 13 years and almost every seventh student at grade I of the gymnasium were exposed to cyberbullying. There were more students exposed to at least one cyberbullying than to multiple cyberbullying. Potential predictors of exposure to cyberbullying are gender, opinion of the family’s affluence status, fathers’ employment, communication with father, and family support. The study compensates for the evidence of cyberbullying in Serbia, which could help raise awareness, inform national and international stakeholders in the region and enable their efforts and strengthen cooperation in ending cyberbullying. This study’s findings could inform the development of an intervention program aimed at families and various professionals involved in protecting and improving school-age children’s health and well-being.

Genomic Analyses of Pediatric Acute Lymphoblastic Leukemia Ph+ and Ph-Like-Recent Progress in Treatment.

Pediatric acute lymphoblastic leukemia (ALL) with t(9;22)(q34;q11.2) is a very rare malignancy in children. Approximately 3–5% of pediatric ALL patients present with the Philadelphia chromosome. Previously, children with Ph+ had a poor prognosis, and were considered for allogeneic stem cell transplantation (allo-HSCT) in their first remission (CR1). Over the last few years, the treatment of childhood ALL has significantly improved due to standardized research protocols. Hematopoietic stem cell transplantation (HSCT) has been the gold standard therapy in ALL Ph+ patients, but recently first-generation tyrosine kinase inhibitor (TKI)-imatinib became a major milestone in increasing overall survival. Genomic analyses give the opportunity for the investigation of new fusions or mutations, which can be used to establish effective targeted therapies. Alterations of the IKZF1 gene are present in a large proportion of pediatric and adult ALL Ph+ cases. IKZF1 deletions are present in ~15% of patients without BCR-ABL1 rearrangements. In BCR-ABL1-negative cases, IKZF1 deletions have been shown to have an independent prognostic impact, carrying a three-fold increased risk of treatment failure. The prognostic significance of IKZF1 gene aberrations in pediatric ALL Ph+ is still under investigation. More research should focus on targeted therapies and immunotherapy, which is not associated with serious toxicity in the same way as classic chemotherapy, and on the improvement of patient outcomes. In this review, we provide a molecular analysis of childhood ALL with t(9;22)(q34;q11.2), including the Ph-like subtype, and of treatment strategies.

Ultrasonographic diagnosis of lumbar disc protrusion in adolescents: comparison with MRI results

Degenerative changes in the discs begin already in childhood, as evidenced by histological studies. Purpose – to compare the diagnostic capabilities of US and MRI in identifying and determining the localization of protrusion of the lumbar intervertebral discs in adolescents. Materials and methods. The study involved 74 patients with protrusion of the lumbar intervertebral discs aged 17-21 years: 25 (33.8 %) girls and 39 (66.2 %) boys. All patients complained of pain in the lower back, and when examined by a neuropathologist, some clinical signs of osteochondrosis were revealed. USG of the lumbar spine was performed with a convex transducer with a frequency of 2-5 MHz at levels from L1-L2 to L5-S1 in sagittal and axial projections. MRI was performed on a Magnetom Aera 1.5T apparatus with standard research protocols. Results. According to the results of MRI at the L4-L5 level, protrusion was localized in 27 (36.5 ± 5.6%) cases, at the level of L5-S1 – in 26 (35.1 ± 5.5 %) cases – significantly (P &lt;0, 05) more often than at the level of L3-L4, L2-L3 і L1-L2 (P &lt;0.001), respectively. The coincidence of the results of MRI and USG took place in 72 (97.3 %) cases. In two cases of USG, the picture of L4-L5 and L5-S1 protrusion was interpreted as a hernia. According to the results of MRI, medial localization of disc protrusion was recorded in 31 (41.9 ± 5.7 %) cases, paramedial – in 29 (39.2 ± 5.7 %), and foraminal – in 14 (18.9 ± 4.5 %) cases, and with USG – in 30 (40.5 ± 5.6%), 28 (37.8 ± 5.6 %) and 14 (18.9 ± 4.5 %) cases, respectively. Strengthening of signals (or increased echogenicity) of the nucleus pulposus (NP) was detected on MRI in 61 (82.4 ± 4.4 %) cases, on USG in 56 (77.8 ± 4.9 %) cases; calcification of the NP in 32 (43.2 ± 5.8 %) and 35 (48.6 ± 5.7%); mixing of hyperechogenic NP - in 31 (41.9 ± 5.7 %) and 43 (59.7 ± 5.6%) cases (P &lt;0.05); FR thinning – in 56 (75.7 ± 5.9 %) and 53 (73.6 ± 5.3 %) cases; decrease in the sagittal size of the spinal canal – in 17 (23.0 ± 4.9 %) and 18 (25.0 ± 5.1 %) cases, respectively.