"The anxiety coming up to every scan-It destroyed me": A qualitative study of the lived experience of cytomegalovirus infection during pregnancy.

BACKGROUND: Emerging evidence supporting the use of valaciclovir to reduce fetal infection after maternal primary cytomegalovirus (CMV) infection has stimulated interest in routine CMV serological screening in pregnancy. It is important to understand the healthcare consumer perspective of a CMV infection during pregnancy to minimize unintended harms of screening. METHODS: We conducted a qualitative study using semi-structured interviews with Australian women who had a lived experience of CMV infection following serological testing during pregnancy. Participants were recruited via social media and healthcare consumer networks, and purposively selected to capture a range of perinatal outcomes. Interview transcripts were analyzed using inductive content analysis. RESULTS: Twelve participants were interviewed: 6 had a live birth, 4 had terminations of pregnancy, 1 had a neonatal death and 1 was pregnant at the time of interview. Four major categories emerged from the analysis. Women reported a lack of CMV awareness among themselves, their social networks, and among their health care providers. The participants described their experience as "hard" and "stressful". Uncertainty and variability characterized their clinical decision-making process. The pregnancy and postpartum periods were marked by ongoing anxiety about the long-term impacts of CMV. Women supported screening for CMV, decision making and reproductive choice, but acknowledged that routine testing may not be desired by everyone and may increase stress and terminations of pregnancy. Important coping strategies included obtaining support from partners, family, and other families with lived experience of CMV, as well as having access to knowledgeable and sensitive healthcare professionals. CONCLUSION: Serological diagnosis of maternal CMV infection during pregnancy can have severe and prolonged psychological impacts on parents, regardless of the pregnancy outcome. Improving healthcare professionals' knowledge and public awareness are essential before widespread serological screening can be responsibly introduced. Healthcare administrators that are considering implementing a prenatal screening program for secondary prevention of fetal CMV infection should pay attention to consumer perspectives to minimize unintended harms to women and their families.

Early developmental intervention programmes provided post hospital discharge to prevent motor and cognitive impairment in preterm infants.

BACKGROUND: Infants born preterm are at increased risk of cognitive and motor impairments compared with infants born at term. Early developmental interventions for preterm infants are targeted at the infant or the parent-infant relationship, or both, and may focus on different aspects of early development. They aim to improve developmental outcomes for these infants, but the long-term benefits remain unclear. This is an update of a Cochrane review first published in 2007 and updated in 2012 and 2015. OBJECTIVES: Primary objective To assess the effect of early developmental interventions compared with standard care in prevention of motor or cognitive impairment for preterm infants in infancy (zero to < three years), preschool age (three to < five years), and school age (five to < 18 years). Secondary objective To assess the effect of early developmental interventions compared with standard care on motor or cognitive impairment for subgroups of preterm infants, including groups based on gestational age, birthweight, brain injury, timing or focus of intervention and study quality. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO and trial registries in July 2023. We cross-referenced relevant literature, including identified trials and existing review articles. SELECTION CRITERIA: Studies included randomised, quasi-randomised controlled trials (RCTs) or cluster-randomised trials of early developmental intervention programmes that began within the first 12 months of life for infants born before 37 weeks' gestational age (GA). Interventions could commence as an inpatient but had to include a post discharge component for inclusion in this review. Outcome measures were not prespecified, other than that they had to assess cognitive outcomes, motor outcomes or both. The control groups in the studies could receive standard care that would normally be provided. DATA COLLECTION AND ANALYSIS: Data were extracted from the included studies regarding study and participant characteristics, timing and focus of interventions and cognitive and motor outcomes. Meta-analysis using RevMan was carried out to determine the effects of early developmental interventions at each age range: infancy (zero to < three years), preschool age (three to < five years) and school age (five to < 18 years) on cognitive and motor outcomes. Subgroup analyses focused on GA, birthweight, brain injury, time of commencement of the intervention, focus of the intervention and study quality. We used standard methodological procedures expected by Cochrane to collect data and evaluate bias. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: Forty-four studies met the inclusion criteria (5051 randomly assigned participants). There were 19 new studies identified in this update (600 participants) and a further 17 studies awaiting outcomes. Three previously included studies had new data. There was variability in the focus and intensity of the interventions, participant characteristics, and length of follow-up. All included studies were either single or multicentre trials and the number of participants varied from fewer than 20 to up to 915 in one study. The trials included in this review were mainly undertaken in middle- or high-income countries. The majority of studies commenced in the hospital, with fewer commencing once the infant was home. The focus of the intervention programmes for new included studies was increasingly targeted at both the infant and the parent-infant relationship. The intensity and dosages of interventions varied between studies, which is important when considering the applicability of any programme in a clinical setting. Meta-analysis demonstrated that early developmental intervention may improve cognitive outcomes in infancy (developmental quotient (DQ): standardised mean difference (SMD) 0.27 standard deviations (SDs), 95% confidence interval (CI) 0.15 to 0.40; P < 0.001; 25 studies; 3132 participants, low-certainty evidence), and improves cognitive outcomes at preschool age (intelligence quotient (IQ); SMD 0.39 SD, 95% CI 0.29 to 0.50; P < 0.001; 9 studies; 1524 participants, high-certainty evidence). However, early developmental intervention may not improve cognitive outcomes at school age (IQ: SMD 0.16 SD, 95% CI -0.06 to 0.38; P = 0.15; 6 studies; 1453 participants, low-certainty evidence). Heterogeneity between studies for cognitive outcomes in infancy and preschool age was moderate and at school age was substantial. Regarding motor function, meta-analysis of 23 studies showed that early developmental interventions may improve motor outcomes in infancy (motor scale DQ: SMD 0.12 SD, 95% CI 0.04 to 0.19; P = 0.003; 23 studies; 2737 participants, low-certainty evidence). At preschool age, the intervention probably did not improve motor outcomes (motor scale: SMD 0.08 SD, 95% CI -0.16 to 0.32; P = 0.53; 3 studies; 264 participants, moderate-certainty evidence). The evidence at school age for both continuous (motor scale: SMD -0.06 SD, 95% CI -0.31 to 0.18; P = 0.61; three studies; 265 participants, low-certainty evidence) and dichotomous outcome measures (low score on Movement Assessment Battery for Children (ABC) : RR 1.04, 95% CI 0.82 to 1.32; P = 0.74; 3 studies; 413 participants, low-certainty evidence) suggests that intervention may not improve motor outcome. The main source of bias was performance bias, where there was a lack of blinding of participants and personnel, which was unavoidable in this type of intervention study. Other biases in some studies included attrition bias where the outcome data were incomplete, and inadequate allocation concealment or selection bias. The GRADE assessment identified a lower certainty of evidence in the cognitive and motor outcomes at school age. Cognitive outcomes at preschool age demonstrated a high certainty due to more consistency and a larger treatment effect. AUTHORS' CONCLUSIONS: Early developmental intervention programmes for preterm infants probably improve cognitive and motor outcomes during infancy (low-certainty evidence) while, at preschool age, intervention is shown to improve cognitive outcomes (high-certainty evidence). Considerable heterogeneity exists between studies due to variations in aspects of the intervention programmes, the population and outcome measures utilised. Further research is needed to determine which types of early developmental interventions are most effective in improving cognitive and motor outcomes, and in particular to discern whether there is a longer-term benefit from these programmes.

Relationship Between Prone Skills and Motor-Based Problem-Solving Abilities in Full-Term and Preterm Infants During the First 6 Months of Life.

Motor experiences shape cognitive development in infancy, with the prone position being one such crucial motor experience in the first 6 months of life. Although the motor benefits of the prone position are well-documented, its influence on early cognitive abilities remains insufficiently explored. This study quantified the relationship between prone motor skills and motor-based problem-solving abilities in 48 full-term and preterm infants aged 3-6 months. Prone skills were assessed using the Alberta Infant Motor Scale's prone domain. The Assessment of Problem-Solving in Play was utilized to measure motor-based problem-solving by observing how motor actions were used to solve toys. Advanced prone motor skills were correlated with an increase in sophisticated exploration skills and a concurrent decline in lower order exploration skills in all infants, with correlations being stronger in preterm infants. Notably, a 1-point increase in prone skills was associated with a 1.3-point increase in total motor-based problem-solving abilities in all infants. Our findings provide preliminary evidence for the contribution of prone play to cognitive development in infants, prompting considerations for assessment and intervention strategies. Further research is needed to ascertain if the delayed acquisition of prone motor skills is indicative of poor early problem-solving abilities in preterm infants.

In vivo antiangiogenic effect of nimbolide, trans-chalcone and piperine for use against glioblastoma.

BACKGROUND: Angiogenesis is an important hallmark of Glioblastoma (GBM) marked by elevated vascular endothelial growth factor-A (VEGF-A) and its receptor 2 (VEGFR-2). As previously reported nimbolide (NBL), trans-chalcone (TC) and piperine (PPR) possess promising antiangiogenic activity in several cancers however, their comparative efficacy and mechanism of antiangiogenic activity in GBM against VEGFR-2 has not been elucidated. METHODS: 2D and 3D spheroids cultures of U87 (Uppsala 87 Malignant Glioma) were used for evaluation of non-cytotxoic dose for anti-angiogenic activity. The antiangiogenic effect was investigated by the GBM U87 cell line bearing chick CAM model. Excised U87 xenografts were histologically examined for blood vascular density by histochemistry. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect the presence of avian and human VEGF-A and VEGFR-2 mRNA transcripts. RESULTS: Using 2D and 3D spheroid models, the non-cytotoxic dose of NBL, TC and PPR was ≤ 11 µM. We found NBL, TC and PPR inhibit U87-induced neoangiogenesis in a dose-dependent manner in the CAM stand-alone model as well as in CAM U87 xenograft model. The results also indicate that these natural compounds inhibit the expression of notable angiogenic factors, VEGF-A and VEGFR-2. A positive correlation was found between blood vascular density and VEGF-A as well as VEGFR-2 transcripts. CONCLUSION: Taken together, NBL, TC and PPR can suppress U87-induced neoangiogenesis via a reduction in VEGF-A and its receptor VEGFR-2 transcript expression at noncytotoxic concentrations. These phytochemicals showed their utility as adjuvants to GBM therapy, with Piperine demonstrating superior effectiveness among them all.

Serological screening for cytomegalovirus during pregnancy: A systematic review of clinical practice guidelines and consensus statements.

BACKGROUND: Congenital cytomegalovirus (cCMV) is the most common congenital infection worldwide. cCMV can lead to severe long-term sequelae, including neurological impairment and developmental delay. We performed a systematic review of clinical practice guidelines containing recommendations concerning serological screening for CMV during pregnancy. METHOD: We performed a search of MEDLINE, Turning Research into Practice (TRIP) database and the grey literature for clinical practice guidelines or consensus statements published in the English language from Jan 2010 to June 2022. The quality of the included guidelines was assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. Textual synthesis was used to summarise and compare the recommendations on CMV serological screening in pregnancy. RESULTS: Eleven guidelines and two consensus statements were included. None recommended universal serological screening for CMV in pregnant women; five recommended screening for high-risk women (those with frequent contact with young children). The overall quality of the guidelines varied; most were medium or low. CONCLUSIONS: Although clinical practice guidelines do not actively recommend routine serological screening in pregnancy, most did not meet standard processes for development and predated the emerging data on valaciclovir as a potential intervention. Existing recommendations are underpinned by limited, low-level evidence, exposing the lack of robust data in this area of practice. Further high-level evidence and methodologically robust guidelines are needed to guide clinical practice in this rapidly changing field.

Evaluation of Therapeutic Potential of Selected Plant-Derived Homeopathic Medicines for their Action against Cervical Cancer.

BACKGROUND: Plant-derived homeopathic medicines (HMs) are cheap and commercially available but are mechanistically less explored entities than conventional medicines. PURPOSE: The aim of our study was to evaluate the impact of selected plant-derived HMs derived from Berberis aquifolium (BA), Berberis vulgaris (BV), Mentha piperita (MP), Curcuma longa (CL), Cinchona officinalis (CO), Thuja occidentalis (TO) and Hydrastis canadensis (HC) on cervical cancer (CaCx) cells in vitro. METHODS: We screened the mother tincture (MT) and 30C potencies of the above-mentioned HMs for anti-proliferative and cytotoxic activity on human papillomavirus (HPV)-negative (C33a) and HPV-positive CaCx cells (SiHa and HeLa) by MTT assay. Total phenolic content (TPC) and the free-radical scavenging activity of each HM was also determined using standard assays. Phytochemicals reportedly available in these HMs were examined for their potential inhibitory action on HPV16 E6 by in silico molecular docking. RESULTS: All tested MTs induced a differential dose-dependent cytotoxic response that varied with cell line. For C33a cells, the order of response was TO > CL > BA > BV > HC > MP > CO, whereas for SiHa and HeLa cells the order was HC > MP > TO > CO > BA > BV > CL and CL > BA > CO, respectively. 30C potencies of all HMs showed an inconsistent response. Further, anti-CaCx responses displayed by MTs did not follow the order of an HM's phenolic content or free radical scavenging activity. Analysis revealed anti-oxidant content of BA, BV and HC had the lowest contribution to their anti-CaCx activity. Using in silico modeling of molecular docking between the HPV16 E6 protein crystallographic structures (6SJA and 4XR8) and main phytochemical components of BV, BA, HC, CL and TO, their potential to inhibit the HPV16 E6 protein carcinogenic interactions was identified. CONCLUSION: The study has shown a comparative evaluation of the potential of several plant-derived MTs and HMs to affect CaCx cell line survival in vitro (through cytotoxicity and free radical scavenging) and their theoretical molecular targets in silico for the first time. Data demonstrated that MTs of BA and BV are likely to be the most potent HMs that strongly inhibited CaCx growth and have a strong anti-HPV phytochemical constitution.

Transcriptome analysis of cervical cancer exosomes and detection of HPVE6*I transcripts in exosomal RNA.

BACKGROUND: Exosomes play a key role in cell-to-cell communication and are integral component of the tumor microenvironment. Recent observations suggest transfer of RNA through tumor-derived exosomes that can potentially translate into regulatory proteins in the recipient cells. Role of cervical cancer-derived exosomes and their transcript cargo is poorly understood. MATERIALS AND METHODS: The total RNA of exosomes from HPV-positive (SiHa and HeLa) and HPV-negative (C33a) cervical cancer cell lines were extracted and the transcripts were estimated using Illumina HiSeq X. Further, validation of HPV transcripts were performed using RT-PCR. RESULTS: 3099 transcripts were found to be differentially-exported in HPV-positive vs. HPV-negative exosomes (p value <0.05). Analysis of top 10 GO terms and KEGG pathways showed enrichment of transcripts belonging to axon guidance and tumor innervation in HPV-positive exosomes. Among top 20 overexpressed transcripts, EVC2, LUZP1 and ANKS1B were the most notable due to their involvement in Hh signaling, cellular migration and invasion, respectively. Further, low levels of HPV-specific reads were detected. RT-PCR validation revealed presence of E6*I splice variant of HPV18 in exosomal RNA of HeLa cells. The E6*I transcripts were consistently retained in exosomes obtained from HeLa cells undergoing 5-FU and cisplatin-induced oxidative stress. CONCLUSION: Our data suggests the enrichment of poly-A RNA transcripts in the exosomal cargo of cervical cancer cells, which includes pro-tumorigenic cellular RNA and viral transcripts such as HPV E6, which may have clinical utility as potential exosomal biomarkers of cervical cancer.

Screening and Evaluation of Neurodevelopmental Impairments in Infants Under 6 Months of Age with Congenital Heart Disease.

Clinical evaluation of neurodevelopmental impairments before 6 months of age is needed in congenital heart disease (CHD) to promote early referral to developmental interventions. The objective was to identify the risk of cerebral palsy (CP) and to compare neurodevelopment outcomes in infants with and without CHD. In a longitudinal study, 30 infants with CHD and 15 infants without CHD were assessed at 1 month, 3 months, and 6 months of age. Included measures were General Movement Assessment (GMA), Test of Infant Motor Performance (TIMP) and the Bayley Scale of Infant Development, third edition (Bayley-III), selected to identify the risk of CP, document neurodevelopmental impairments and infants' eligibility for early intervention services. Abnormal GMA categories were found in the CHD group where 48% had poor repertoire and 15% were at high risk of CP. At 3 months of age, CHD group had significantly lower TIMP scores compared to infants without CHD [t(41) = 6.57, p = 0.01]. All infants in the study had higher Bayley-III scores at 6 months than at 3 months of age. Infants with CHD had lower gross motor, fine motor and cognitive Bayley-III scores compared to their peers without CHD. Over time infants without CHD outperformed the CHD group in the gross motor skills [F(1,41) = 11.76, p = .001]. Higher prevalence of abnormal GMs, lower TIMP and Bayley-III were found in infants with single ventricle physiology compared to two-ventricle physiology. The risk of CP exists in infants with CHD, and these infants have worse outcomes compared to their peers without CHD. These differences are intensified in the single ventricle population.Clinical Trial Registration National Institute of Health, Unique identifier: NCT03104751; Date of registration-April 7, 2017.

Identification of the conserved long non-coding RNAs in myogenesis.

BACKGROUND: Our understanding of genome regulation is ever-evolving with the continuous discovery of new modes of gene regulation, and transcriptomic studies of mammalian genomes have revealed the presence of a considerable population of non-coding RNA molecules among the transcripts expressed. One such non-coding RNA molecule is long non-coding RNA (lncRNA). However, the function of lncRNAs in gene regulation is not well understood; moreover, finding conserved lncRNA across species is a challenging task. Therefore, we propose a novel approach to identify conserved lncRNAs and functionally annotate these molecules. RESULTS: In this study, we exploited existing myogenic transcriptome data and identified conserved lncRNAs in mice and humans. We identified the lncRNAs expressing differentially between the early and later stages of muscle development. Differential expression of these lncRNAs was confirmed experimentally in cultured mouse muscle C2C12 cells. We utilized the three-dimensional architecture of the genome and identified topologically associated domains for these lncRNAs. Additionally, we correlated the expression of genes in domains for functional annotation of these trans-lncRNAs in myogenesis. Using this approach, we identified conserved lncRNAs in myogenesis and functionally annotated them. CONCLUSIONS: With this novel approach, we identified the conserved lncRNAs in myogenesis in humans and mice and functionally annotated them. The method identified a large number of lncRNAs are involved in myogenesis. Further studies are required to investigate the reason for the conservation of the lncRNAs in human and mouse while their sequences are dissimilar. Our approach can be used to identify novel lncRNAs conserved in different species and functionally annotated them.

Exosomes from cervical cancer cells facilitate pro-angiogenic endothelial reconditioning through transfer of Hedgehog-GLI signaling components.

BACKGROUND: Angiogenic switch is a hallmark feature of transition from low-grade to high-grade cervical intraepithelial neoplasia (CIN) in cervical cancer progression. Therefore, early events leading to locally-advanced cervical metastatic lesions demand a greater understanding of the underlying mechanisms. Recent leads indicate the role of tumor-derived exosomes in altering the functions of endothelial cells in cervical cancer, which needs further investigation. METHODS: Exosomes isolated from cervical cancer cell lines were assessed for their angiogenic effect on the human umbilical vein endothelial cells (HUVEC) using tube formation and wound healing assay. The exosomal uptake by HUVEC cells was monitored using PKH-67 labelling followed by fluorescence microscopy. Alterations in Hh-GLI signaling components, PTCH1 and GLI1, in HUVEC were measured by immunoblotting. Changes in angiogenesis-related transcripts of vascular endothelial growth factor VEGF-A, VEGF-B, VEGFR2 and angiopoietin-1, angiopoietin-2, osteopontin were measured in exosome-treated HUVEC and in the exosomal RNA by RT-PCR. RESULTS: Enhanced tube formation, with an increased number of nodes and branching was observed in HUVEC's treated with exosomes derived from different cervical cancer cell lines. HPV-positive (SiHa and HeLa) cells' exosomes were more angiogenic. Exosome-treated HUVEC showed increased migration rate. PKH-67 labelled exosomes were found internalized in HUVEC. A high level of PTCH1 protein was detected in the exosome-treated endothelial cells. Subsequent RT-PCR analysis showed increased transcripts of Hh-GLI downstream target genes VEGF-A, VEGFR2, angiopoietin-2, and decreased expression of VEGF-B, and angiopoietin-1, suggestive of active Hh-GLI signaling. These effects were more pronounced in HUVEC's treated with exosomes of HPV-positive cells. However, these effects were independent of tumor-derived VEGF-A as exosomal cargo lacked VEGF-A transcripts or proteins. CONCLUSION: Overall, the data showed cervical cancer exosomes promote pro-angiogenic response in endothelial cells via upregulation of Hh-GLI signaling and modulate downstream angiogenesis-related target genes. The study provides a novel exosome-mediated mechanism potentially favoring cervical angiogenesis and thus identifies the exosomes as potential pharmacological targets against locally-advanced metastatic cervical lesions.

Early motor skills predict the developmental trajectory of problem solving in young children with motor delays.

INTRODUCTION: The purpose of this study was to quantify the relationship between early motor skills, such as sitting, and the development of problem-solving skills in children with motor delays. METHODS: Motor (Gross Motor Function Measure) and problem-solving (Assessment of Problem-Solving in Play) skills of 134 children 7-16 months adjusted age at baseline with motor delay were assessed up to 5 times over 12 months. Participants were divided into two groups: mild and significant motor delay. RESULTS: Motor and problem-solving scores had large (r's = 0.53-0.67) and statistically significant (p's > .01) correlations at all visits. Baseline motor skills predicted baseline and change in problem solving over time. The associations between motor and problem-solving skills were moderated by level of motor delay, with children with significant motor delay generally having stronger associations compared to those with mild motor delay. CONCLUSIONS: These findings suggest that overall baseline motor skills are predictive of current and future development of problem-solving skills and that children with significant motor delay have a stronger and more stable association between motor and problem-solving skills over time. This highlights that children with motor delays are at risk for secondary delays in problem solving, and this risk increases as degree of motor delay increases.

Measuring Early Problem-Solving in Young Children with Motor Delays: A Validation Study.

AIM: There is a lack of evidence-based tools for measuring problem-solving in young children with motor delays. The purpose of this study was to evaluate the construct validity and responsiveness of the Assessment of Problem-Solving in Play. METHODS: 125 young children (10.72, SD 2.62 months) with mild, moderate, and severe motor delays were assessed with the Bayley Scales of Infant and Toddler Development, Third Edition Cognitive Scale and the Assessment of Problem-Solving in Play up to 4 times over 12 months. The baseline and change over time assessment scores were compared. RESULTS: The Assessment of Problem-Solving in Play was strongly, positively correlated with the Bayley Scales of Infant and Toddler Development, Third Edition Cognitive Scale raw scores at baseline (r=.83, p<.001) and for changes in scores across time (r=.64, p<.001). On average, participants demonstrated positive change in problem-solving scores across time. Participants with severe motor delay scored lower at baseline and changed less as compared to other participants. CONCLUSIONS: Results provide evidence for the construct validity and responsiveness of the Assessment of Problem-Solving in Play scores in quantifying problem-solving in young children with motor delays 7-27 months of age.

Collecting Infant Environmental and Experiential Data Using Smartphone Surveys.

We propose that the collection of infant experiential and environmental data using smartphone surveys has the potential to fill a gap in foundational and clinical knowledge. To achieve this, these data need to be collected in a systematic way that is translatable globally. We can then begin to understand differences in child development and physical therapy from a variety of cultures and traditions. An infant's development is shaped by experiences in everyday life, and everyday experiences vary around the world. Hence, it is important to quantify these experiences to better understand variability in developmental trajectories. Recent increase in smartphone access has made the capability of collecting infant experiential data more feasible around the world. We provide examples and suggestions for ways in which experiential and environmental data can be collected for future practice.

Sitting skill and the emergence of arms-free sitting affects the frequency of object looking and exploration.

The development of sitting changes how much infants are able to explore objects. Infants who can sit with their arms free are likely to explore their environment more effectively than prop sitters, as their hands are free to explore. We sought to quantify how prop sitters differed in the amount of visual and manual exploration of objects from arms-free sitters. Infants younger than 7 months (n = 31) were recruited at sitting emergence, either prop or arms-free sitting without the ability to change positions. Infants were grouped into sitting stages at baseline: prop (n = 17) or wobbly/arms-free (n = 14). Across three visits (baseline, 3 weeks later, 6-8 weeks later), researchers assessed the infants' total gross motor skill, sitting skill, and object looking and active exploration. Infants' gross motor and sitting skill was assessed using the Gross Motor Function Measure (GMFM)-66 total scores and GMFM-88 sitting dimension scores. While researchers supported infants in sitting, object looking and exploration were assessed using a series of three object exploration tasks and scoring modified slightly from the Early Problem Solving Indicator at each visit. Differences between trajectories of prop and wobbly/arms-free sitters for the frequencies of two behaviors, looks and explores, were analyzed using longitudinal multilevel modeling. Prop sitters initially explored toys less frequently, but increased their exploration more quickly, than wobbly/arms-free sitters. Sitting skill predicted minor changes in the development of looking; both stage and skill predicted changes uniquely in the development of exploration. These findings suggest that independent, arms-free sitting changes how capable infants are of exploring objects visually and manually.

Supporting play exploration and early developmental intervention versus usual care to enhance development outcomes during the transition from the neonatal intensive care unit to home: a pilot randomized controlled trial.

BACKGROUND: While therapy services may start in the Neonatal Intensive Care Unit (NICU) there is often a gap in therapy after discharge. Supporting Play Exploration and Early Development Intervention (SPEEDI) supports parents, helping them build capacity to provide developmentally supportive opportunities starting in the NICU and continuing at home. The purpose of this single blinded randomized pilot clinical trial was to evaluate the initial efficacy of SPEEDI to improve early reaching and exploratory problem solving behaviors. METHODS: Fourteen infants born very preterm or with neonatal brain injury were randomly assigned to SPEEDI or Usual Care. The SPEEDI group participated in 5 collaborative parent, therapist, and infant interventions sessions in the NICU (Phase 1) and 5 at home (Phase 2). Parents provided daily opportunities designed to support the infants emerging motor control and exploratory behaviors. Primary outcome measures were assessed at the end of the intervention, 1 and 3 months after the intervention ended. Reaching was assessed with the infant supported in an infant chair using four 30 s trials. The Early Problem Solving Indicator was used to evaluate the frequency of behaviors during standardized play based assessment. Effect sizes are including for secondary outcomes including the Test of Infant Motor Performance and Bayley Scales of Infant and Toddler Development. RESULTS: No group differences were found in the duration of toy contact. There was a significant group effect on (F1,8 = 4.04, p = 0.08) early exploratory problem-solving behaviors with infants in the SPEEDI group demonstrating greater exploration with effect sizes of 1.3, 0.6, and 0.9 at the end of the intervention, 1 and 3 months post-intervention. CONCLUSIONS: While further research is needed, this initial efficacy study showed promising results for the ability of SPEEDI to impact early problem solving behaviors at the end of intervention and at least 3 months after the intervention is over. While reaching did not show group differences, a ceiling effect may have contributed to this finding. This single blinded pilot RCT was registered prior to subject enrollment on 5/27/14 at ClinicalTrials.Gov with number NCT02153736.

Targeting Cervical Cancer Stem Cells by Phytochemicals.

Cervical cancer (CaCx) poses a significant global health challenge, ranking as the fourth most common cancer among women worldwide. Despite the emergence of advanced treatment strategies, recurrence remains a bottleneck in favorable treatment outcomes and contributes to poor prognosis. The chemo- or radio-therapy resistance coupled with frequent relapse of more aggressive tumors are some key components that contribute to CaCx-related mortality. The onset of therapy resistance and relapse are attributed to a small subset of, slow-proliferating Cancer Stem Cells (CSC). These CSCs possess the properties of tumorigenesis, self-renewal, and multi-lineage differentiation potential. Because of slow cycling, these cells maintain themselves in a semi-quiescent stage and protect themselves from different anti-proliferative anti-cancer drugs. Keeping in view recent advances in their phenotypic and functional characterization, the feasibility of targeting CSC and associated stem cell signaling bears a strong translational value. The presence of CSC has been reported in CaCx (CCSC) which remains a forefront area of research. However, we have yet to identify clinically useful leads that can target CCSC. There is compelling evidence that phytochemicals, because of their advantages over synthetic anticancer drugs, could emerge as potential therapeutic leads to target these CCSCs. The present article examined the potential of phytochemicals with reported anti-CSC properties and evaluated their future in preclinical and clinical applications against CaCx.

Prognostic and therapeutic potential of STAT3: Opportunities and challenges in targeting HPV-mediated cervical carcinogenesis.

Cervical cancer (CaCx) ranks as the fourth most prevalent cancer among women globally. Persistent infection of high-risk human papillomaviruses (HR-HPVs) is major etiological factor associated with CaCx. Signal Transducer and Activator of Transcription 3 (STAT3), a prominent member of the STAT family, has emerged as independent oncogenic driver. It is a target of many oncogenic viruses including HPV. How STAT3 influences HPV viral gene expression or gets affected by HPV is an area of active investigation. A better understanding of host-virus interaction will provide a prognostic and therapeutic window for CaCx control and management. In this comprehensive review, we delve into carcinogenic role of STAT3 in development of HPV-induced CaCx. With an emphasis on fascinating interplay between STAT3 and HPV genome, the review explores the diverse array of opportunities and challenges associated with this field to harness the prognostic and therapeutic potential of STAT3 in CaCx.

Manual Abilities and Cognition in Children with Cerebral Palsy: Do Fine Motor Skills Impact Cognition as Measured by the Bayley Scales of Infant Development?

Manual ability may be an important consideration when measuring cognition in children with CP because many items on cognitive tests require fine motor skills. This study investigated the association of fine motor dependent (FMD) and fine motor independent (FMI) items within the cognitive domain (COG) of the Bayley Scales of Infant Development-Third Edition (Bayley-III) and Manual Ability Classification System (MACS) in children with cerebral palsy. Children aged 2 to 8 (3.96 ± 1.68) years were included in this study. MACS levels were assigned at baseline. COG was administrated at baseline (n = 61) and nine months post-baseline (n = 28). The 91 items were classified into FMD (52) and FMI (39). Total raw score, FMD, and FMI scores were calculated. The association between MACS and cognitive scores (total, FMD, and FMI) were evaluated using linear regression and Spearman correlation coefficients. We found total, FMD, and FMI scores decrease significantly as the MACS level increases at the baseline. Both FMD and FMI scores decreased as MACS levels increased (worse function). There was a significant difference between the two slopes, with the FMD scores having a steeper slope. Similar patterns were observed nine months post-baseline. Children with lower manual ability scored lower in the cognitive domain at baseline and 9 months post-baseline. The significant difference in the performance of FMD items and FMI items across MACS levels with a steeper slope of changes in FMD items suggests fine motor skills impact cognition.

To speak may draw on epigenetic writing and reading: Unravelling the complexity of speech and language outcomes across chromatin-related neurodevelopmental disorders.

Speech and language development are complex neurodevelopmental processes that are incompletely understood, yet current evidence suggests that speech and language disorders are prominent in those with disorders of chromatin regulation. This review aimed to unravel what is known about speech and language outcomes for individuals with chromatin-related neurodevelopmental disorders. A systematic literature search following PRISMA guidelines was conducted on 70 chromatin genes, to identify reports of speech/language outcomes across studies, including clinical reports, formal subjective measures, and standardised/objective measures. 3932 studies were identified and screened and 112 were systematically reviewed. Communication impairment was core across chromatin disorders, and specifically, chromatin writers and readers appear to play an important role in motor speech development. Identification of these relationships is important because chromatin disorders show promise as therapeutic targets due to the capacity for epigenetic modification. Further research is required using standardised and formal assessments to understand the nuanced speech/language profiles associated with variants in each gene, and the influence of chromatin dysregulation on the neurobiology of speech and language development.

A Rare Case of Metastatic Small Cell Carcinoma of Lung in a Follow-Up Patient of Chronic Myeloid Leukemia on Imatinib Treatment.

Imatinib has an excellent long-term survival rate and significantly ameliorates the treatment of chronic myeloid leukaemia during the past few decades. There is now a concern that first-generation tyrosine kinase inhibitors can cause secondary neoplasms. Here, we describe a case of a 49-year-old non-smoker male who was diagnosed with chronic myeloid leukaemia and treated with imatinib. After 15 years of treatment, an incidental right cervical lymphadenopathy was noted. The fine needle aspiration cytology from the lymph node revealed the small round cell morphology. In order to identify the primary lesion, computerised tomography of the thorax and abdomen was advised, which revealed a diagnosis of small cell carcinoma lung. In the index case report, we will discuss the potential side effects of first-generation tyrosine kinase inhibitors on a long-term basis along with treatment protocols for metastatic small cell carcinoma lung in a disease-free follow-up case of chronic myeloid leukaemia.