Mikania micrantha silver nanoparticles exhibit anticancer activities against human lung adenocarcinoma via caspase-mediated apoptotic cell death.

Green-mediated synthesis of nanoparticles has earned a promising role in the area of nanotechnology due to their biomedical applications. This study describes the synthesis of silver nanoparticles (AgNPs) using Mikania micrantha leaf extract and its functional activities against cancer. The synthesis of AgNPs was confirmed using Ultraviolet-Visible (UV-Vis) spectrum that exhibited an absorption band at 459 nm. The bioactive compounds of M. micrantha leaf extract that functioned as reducing and capping agents were confirmed by a shift in the absorption bands in Fourier Transform Infra-red Spectroscopy (FT-IR). Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) studies validated the spherical shape and size of AgNPs, respectively. Energy Dispersive Spectroscopy (EDS) analysis revealed the presence of elemental silver. The crystalline nature of AgNPs was confirmed by the X-ray Diffraction Analysis (XRD). AgNPs effectively induced cytotoxicity and prevented A549 cell colony formation in a dose-dependent manner. Treatment of A549 cells with AgNPs also increased DNA damage, which was coupled with elevated lipid peroxidation and decreased antioxidant enzymes such as glutathione (GSH), glutathione-s-transferase (GST), and superoxide dismutase (SOD). Following AgNPs treatment, the mRNA expression levels of the pro-apoptotic genes as well as the activities of caspases were significantly elevated in A549 cells while the expression levels of anti-apoptotic genes were downregulated. Our study demonstrates the potential of the synthesised AgNPs for cancer therapy possibly targeting the apoptotic pathway.

Highly parallel and ultra-low-power probabilistic reasoning with programmable gaussian-like memory transistors.

Probabilistic inference in data-driven models is promising for predicting outputs and associated confidence levels, alleviating risks arising from overconfidence. However, implementing complex computations with minimal devices still remains challenging. Here, utilizing a heterojunction of p- and n-type semiconductors coupled with separate floating-gate configuration, a Gaussian-like memory transistor is proposed, where a programmable Gaussian-like current-voltage response is achieved within a single device. A separate floating-gate structure allows for exquisite control of the Gaussian-like current output to a significant extent through simple programming, with an over 10000 s retention performance and mechanical flexibility. This enables physical evaluation of complex distribution functions with the simplified circuit design and higher parallelism. Successful implementation for localization and obstacle avoidance tasks is demonstrated using Gaussian-like curves produced from Gaussian-like memory transistor. With its ultralow-power consumption, simplified design, and programmable Gaussian-like outputs, our 3-terminal Gaussian-like memory transistor holds potential as a hardware platform for probabilistic inference computing.

Bright daylight produces negative effects on affective and cognitive outcomes in nocturnal rats.

The daily light/dark cycle affects animals' learning, memory, and cognition. Exposure to insufficient daylight illumination negatively impacts emotion and cognition, leading to seasonal affective disorder characterized by depression, anxiety, low motivation, and cognitive impairment in diurnal animals. However, how this affects memory, learning, and cognition in nocturnal rodents is largely unknown. Here, we studied the effect of daytime light illuminance on memory, learning, cognition, and expression of mRNA levels in the hippocampus, thalamus, and cortex, the higher-order learning centers. Two experiments were performed. In experiment one, rats were exposed to 12 L:12D (12 h light and 12 h dark) with a 10, 100, or 1000 lx daytime light illuminance. After 30 days, various behavioral tests (novel object recognition test, hole board test, elevated plus maze test, radial arm maze, and passive avoidance test) were performed. In experiment 2, rats since birth were raised either under constant bright light (250 lx; LL) or a daily light-dark cycle (12 L:12D). After four months, behavioral tests (novel object recognition test, hole board test, elevated plus maze test, radial arm maze, passive avoidance test, Morris water maze, and Y-maze tests) were performed. At the end of experiments, rats were sampled, and mRNA expression of Brain-Derived Neurotrophic Factor (Bdnf), Tyrosine kinase (Trk), microRNA132 (miR132), Neurogranin (Ng), Growth Associated Protein 43 (Gap-43), cAMP Response Element-Binding Protein (Crebp), Glycogen synthase kinase-3ß (Gsk3ß), and Tumour necrosis factor-α (Tnf-α) were measured in the hippocampus, cortex, and thalamus of individual rats. Our results show that exposure to bright daylight (100 and 1000 lx; experiment 1) or constant light (experiment 2) compromises memory, learning, and cognition. Suppressed expression levels of these mRNA were also observed in the hypothalamus, cortex, and thalamus. These results suggest that light affects differently to different groups of animals.

Restraint stress-induced effects on learning, memory, cognition, and expression of transcripts in different brain regions of mice.

BACKGROUND: Stress is one of the prevalent factors influencing cognition. Several studies examined the effect of mild or chronic stress on cognition. However, most of these studies are limited to a few behavioral tests or the expression of selected RNA/proteins markers in a selected brain region. METHODS: This study examined the effect of restraint stress on learning, memory, cognition, and expression of transcripts in key learning centers. Male mice were divided into three groups (n = 6/group)-control group, stress group (adult stressed group; S), and F1 group (parental stressed group). Stress group mice were subjected to physical restraint stress for 2 h before light offset for 2 weeks. The F1 group comprised adult male mice born of stressed parents. All animals were subjected to different tests and were sacrificed at the end. Transcription levels of Brain-Derived Neurotrophic Factor (Bdnf), Tyrosine kinase (TrkB), Growth Associated Protein 43 (Gap-43), Neurogranin (Ng), cAMP Response Element-Binding Protein (Creb), Glycogen synthase kinase-3ß (Gsk3ß), Interleukine-1 (IL-1) and Tumour necrosis factor-α (Tnf-α) were studied. RESULTS: Results show that both adult and parental stress negatively affect learning, memory and cognition, as reflected by taking longer time to achieve the task or showing reduced exploratory behavior. Expression of Bdnf, TrkB, Gsk3ß and Ng was downregulated, while IL-1 and Tnf-α were upregulated in the brain's cortex, thalamus, and hippocampus region of stressed mice. These effects seem to be relatively less severe in the offspring of stressed parents. CONCLUSIONS: The findings suggest that physical restraint stress can alter learning, memory, cognition, and expression of transcripts in key learning centers of brain.

Probiotics for the postoperative management of term neonates after gastrointestinal surgery.

BACKGROUND: The intestinal microflora has an essential role in providing a barrier against colonisation of pathogens, facilitating important metabolic functions, stimulating the development of the immune system, and maintaining intestinal motility. Probiotics are live microorganisms that can be administered to supplement the gut flora. Neonates who have undergone gastrointestinal surgery are particularly susceptible to infectious complications in the postoperative period. This may be partly due to a disruption of the integrity of the gut and its intestinal microflora. There may be a role for probiotics in reducing the incidence of sepsis and improving intestinal motility, thus reducing morbidity and mortality and improving enteral feeding in neonates in the postoperative period. OBJECTIVES: To evaluate the efficacy and safety of administering probiotics after gastrointestinal surgery for the postoperative management of neonates born from 35 weeks of gestation. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and trial registries in August 2023. We checked reference lists of included studies and relevant systematic reviews for additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that investigated the postoperative administration of oral probiotics versus placebo or no treatment in neonates born from 35 weeks of gestation who had one or more gastrointestinal surgical procedures. We applied no restrictions regarding the type or dosage of probiotics or the duration of treatment. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods, and we used GRADE to assess the certainty of evidence. MAIN RESULTS: We identified one RCT that recruited 61 neonates with a gestational age of 35 weeks or more. All infants were admitted to a neonatal intensive care unit and had surgery for gastrointestinal pathologies. There may be little or no difference in proven sepsis (positive bacterial culture, local or systemic) between infants who receive probiotics compared with those who receive placebo (odds ratio (OR) 0.64, 95% confidence interval (CI) 0.16 to 2.55; 61 infants; low-certainty evidence). Probiotics compared to placebo may have little or no effect on time to full enteral feeds (mean difference (MD) 0.63 days, 95% CI -4.02 to 5.28; 61 infants; low-certainty evidence). There were no reported deaths prior to discharge from hospital in either study arm. Two weeks after supplementation, the infants who received probiotics had a substantially higher relative abundance of non-pathogenic intestinal microflora (Bifidobacteriaceae) than those who received placebo (MD 38.22, 95% CI 28.40 to 48.04; 39 infants; low-certainty evidence). AUTHORS' CONCLUSIONS: This review provides low-certainty evidence from one small RCT that probiotics compared to placebo have little or no effect on the risk of proven sepsis (positive bacterial culture, local or systemic) or time to full-enteral feeds in neonates who have undergone gastrointestinal surgery. Probiotics may substantially increase the abundance of beneficial bacterial in the intestine of these neonates, but the clinical implications of this finding are unknown. There is a need for adequately powered RCTs to assess the role of probiotics in this population. We identified two ongoing studies. As neither reported the gestational age of prospective study participants, we are unsure if they will be eligible for inclusion in this review.

Early versus late administration of amino acids in preterm infants receiving parenteral nutrition.

BACKGROUND: Observational studies in preterm newborns suggest that delay in administering amino acids (AA) could result in a protein catabolic state and impact on growth and development. OBJECTIVES: The objective of this review was to compare the efficacy and safety of early versus late administration of intravenous AA in neonates born at < 37 weeks of gestation. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and trial registries in March 2023. We checked the reference lists of included studies and studies/systematic reviews where subject matter related to the intervention or population examined in this review. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing early administration of AA with late administration in premature newborn infants. We defined early administration of AA solution as the administration of AA in isolation or with total parenteral nutrition within the first 24 hours of birth, and late administration as the administration of AA in isolation or with total parenteral nutrition after the first 24 hours of birth. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. We used the GRADE approach to assess the certainty of the evidence. MAIN RESULTS: Nine studies (383 participants) were eligible for inclusion in the review. All study participants were born at < 37 weeks of gestation and were inpatients in neonatal intensive care units. No studies reported growth during the first months of life as assessed by difference in weight. Early administration of AA may have little or no effect on growth in the first month of life as measured by length (mean difference (MD) 0.00, 95% confidence interval (CI) -0.41 to 0.41; 1 study; 21 participants; low-certainty evidence) and head circumference (MD 0.05, 95% CI -0.03 to 0.14; 2 studies; 87 participants; low-certainty evidence). No studies reported the discharge weight outcome. Early administration of AA may result in little to no difference in neurodevelopmental outcome assessed by Mental Developmental Index (MDI) of < 70 at two years of age (odds ratio 0.83, 95% CI 0.21 to 3.28; 1 study; 111 participants; low-certainty evidence). No studies reported all-cause mortality at 28 days and before discharge. Early administration of AA may result in a large increase in positive nitrogen balance in the first three days of life (MD 250.42, 95% CI 224.91 to 275.93; 4 studies; 93 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: Low-certainty evidence suggests that there may be little to no difference between early and late administration of AA in growth (measured by length and head circumference during the first month after birth) and neurodevelopmental outcome (assessed by MDI of < 70). No RCTs reported on weight in the first month of life, mortality (all-cause mortality at 28 days and before discharge), or discharge weight. Low-certainty evidence suggests a large increase in positive nitrogen balance in preterm infants who received AA within 24 hours of birth. The clinical relevance of this observation is unknown. The number of infants in the RCTs included in the review was small, and there was clinical heterogeneity amongst trials. Adequately powered trials in infants < 37 weeks' gestation are required to determine optimal timing of initiation of AA. We identified two ongoing studies. Both studies will be recruiting infants ≥ 34 weeks of gestation and may or may not add to the outcome data for this review.

Comparison of simultaneous auscultation and ultrasound for clinical assessment of bowel peristalsis in neonates.

Introduction: Assessment of bowel health in ill preterm infants is essential to prevent and diagnose early potentially life-threatening intestinal conditions such as necrotizing enterocolitis. Auscultation of bowel sounds helps assess peristalsis and is an essential component of this assessment. Aim: We aim to compare conventional bowel sound auscultation using acoustic recordings from an electronic stethoscope to real-time bowel motility visualized on point-of-care bowel ultrasound (US) in neonates with no known bowel disease. Methods: This is a prospective observational cohort study in neonates on full enteral feeds with no known bowel disease. A 3M™ Littmann® Model 3200 electronic stethoscope was used to obtain a continuous 60-s recording of bowel sounds at a set region over the abdomen, with a concurrent recording of US using a 12l high-frequency Linear probe. The bowel sounds heard by the first investigator using the stethoscope were contemporaneously transferred for a computerized assessment of their electronic waveforms. The second investigator, blinded to the auscultation findings, obtained bowel US images using a 12l Linear US probe. All recordings were analyzed for bowel peristalsis (duration in seconds) by each of the two methods. Results: We recruited 30 neonates (gestational age range 27-43 weeks) on full enteral feeds with no known bowel disease. The detection of bowel peristalsis (duration in seconds) by both methods (acoustic and US) was reported as a percentage of the total recording time for each participant. Comparing the time segments of bowel sound detection by digital stethoscope recording to that of the visual detection of bowel movements in US revealed a median time of peristalsis with US of 58%, compared to 88.3% with acoustic assessment (p < 0.002). The median regression difference was 26.7% [95% confidence interval (CI) 5%-48%], demonstrating no correlation between the two methods. Conclusion: Our study demonstrates disconcordance between the detection of bowel sounds by auscultation and the detection of bowel motility in real time using US in neonates on full enteral feeds and with no known bowel disease. Better innovative methods using artificial intelligence to characterize bowel sounds, integrating acoustic mapping with sonographic detection of bowel peristalsis, will allow us to develop continuous neonatal bowel sound monitoring devices.

Heterogeneity and Gaps in Reporting Primary Outcomes From Neonatal Trials.

OBJECTIVES: Clear outcome reporting in clinical trials facilitates accurate interpretation and application of findings and improves evidence-informed decision-making. Standardized core outcomes for reporting neonatal trials have been developed, but little is known about how primary outcomes are reported in neonatal trials. Our aim was to identify strengths and weaknesses of primary outcome reporting in recent neonatal trials. METHODS: Neonatal trials including ≥100 participants/arm published between 2015 and 2020 with at least 1 primary outcome from a neonatal core outcome set were eligible. Raters recruited from Cochrane Neonatal were trained to evaluate the trials' primary outcome reporting completeness using relevant items from Consolidated Standards of Reporting Trials 2010 and Consolidated Standards of Reporting Trials-Outcomes 2022 pertaining to the reporting of the definition, selection, measurement, analysis, and interpretation of primary trial outcomes. All trial reports were assessed by 3 raters. Assessments and discrepancies between raters were analyzed. RESULTS: Outcome-reporting evaluations were completed for 36 included neonatal trials by 39 raters. Levels of outcome reporting completeness were highly variable. All trials fully reported the primary outcome measurement domain, statistical methods used to compare treatment groups, and participant flow. Yet, only 28% of trials fully reported on minimal important difference, 24% on outcome data missingness, 66% on blinding of the outcome assessor, and 42% on handling of outcome multiplicity. CONCLUSIONS: Primary outcome reporting in neonatal trials often lacks key information needed for interpretability of results, knowledge synthesis, and evidence-informed decision-making in neonatology. Use of existing outcome-reporting guidelines by trialists, journals, and peer reviewers will enhance transparent reporting of neonatal trials.

Strengthening Reporting of Neonatal Trials.

BACKGROUND AND OBJECTIVES: There is variability in the selection and reporting of outcomes in neonatal trials with key information frequently omitted. This can impact applicability of trial findings to clinicians, families, and caregivers, and impair evidence synthesis. The Neonatal Core Outcomes Set describes outcomes agreed as clinically important that should be assessed in all neonatal trials, and Consolidated Standards of Reporting Trials (CONSORT)-Outcomes 2022 is a new, harmonized, evidence-based reporting guideline for trial outcomes. We reviewed published trials using CONSORT-Outcomes 2022 guidance to identify exemplars of neonatal core outcome reporting to strengthen description of outcomes in future trial publications. METHODS: Neonatal trials including >100 participants per arm published between 2015 to 2020 with a primary outcome included in the Neonatal Core Outcome Set were identified. Primary outcome reporting was reviewed using CONSORT 2010 and CONSORT-Outcomes 2022 guidelines by assessors recruited from Cochrane Neonatal. Examples of clear and complete outcome reporting were identified with verbatim text extracted from trial reports. RESULTS: Thirty-six trials were reviewed by 39 assessors. Examples of good reporting for CONSORT 2010 and CONSORT-Outcomes 2022 criteria were identified and subdivided into 3 outcome categories: "survival," "short-term neonatal complications," and "long-term developmental outcomes" depending on the core outcomes to which they relate. These examples are presented to strengthen future research reporting. CONCLUSIONS: We have identified examples of good trial outcome reporting. These illustrate how important neonatal outcomes should be reported to meet the CONSORT 2010 and CONSORT-Outcomes 2022 guidelines. Emulating these examples will improve the transmission of information relating to outcomes and reduce associated research waste.

Growth and risk of adverse neuro-developmental outcome in newborns with congenital heart disease: A single-centre retrospective study.

BACKGROUND: Mortality in infants with CHD is decreasing and focus has shifted to improving long-term outcomes. Growth and neurodevelopmental outcomes are important long-term endpoints for both clinicians and parents. OBJECTIVE: To evaluate growth and determine the impact of growth on neurodevelopmental outcomes at one year of age in infants who had an operative or therapeutic catheter procedure for CHD in neonatal period. METHODS: This was a single-centre retrospective cohort study of infants born at term gestation with CHD. Demographic details, measurements of growth, and scores of Bayley Scales of Infant and Toddler Assessment (third edition), were collected. Enrolled study participants were categorised in subgroups based on the procedures required prior to one-year assessment. Regression analysis was performed to explore predictive ability of anthropometric measurements on mean scores of developmental assessment. RESULTS: A total of 184 infants were included in the study. Mean z-scores for weight and head circumference at birth were age-appropriate. Mean scores for various developmental domains ranged from borderline to normal except for infants with single ventricular physiology who had gross motor delay concomitant with growth failure. In this group, z-score of weight at one-year-assessment predicted mean score of cognition (p-value 0.02), fine motor (p-value 0.03) and gross motor nearly (p-value 0.06). CONCLUSIONS: Infants born at term gestation, with CHD, without genetic diagnosis had normal fetal growth. Postnatal growth restriction and developmental delay was most marked in infants with single ventricle physiology, suggesting careful nutritional and developmental monitoring.

Light at night: effect on the daily clock, learning, memory, cognition, and expression of transcripts in different brain regions of rat.

The rapid increase in urbanization is altering the natural composition of the day-night light ratio. The light/dark cycle regulates animal learning, memory, and mood swings. A study was conducted to examine the effect of different quantity and quality of light at night on the daily clock, learning, memory, cognition, and expression of transcripts in key learning centers. Treatment was similar for experiments one to three. Rats were exposed for 30 days to 12 h light and 12 h dark with a night light of 2 lx (dLAN group), 250 lx (LL), or without night light (LD). In experiment one, after 28 days, blood samples were collected and 2 days later, animals were exposed to constant darkness. In experiment two, after 30 days of treatment, animals were subjected to various tests involving learning, memory, and cognition. In experiment three, after 30 days of treatment, animals were sampled, and transcript levels of brain-derived neurotrophic factor, tyrosine kinase, Growth-Associated Protein 43, Neurogranin, microRNA-132, cAMP Response Element-Binding Protein, Glycogen synthase kinase-3ß, and Tumor necrosis factor α were measured in hippocampus, thalamus, and cortex tissues. In experiment four, animals were exposed to night light of 0.019 W/m2 but of either red (640 nm), green (540 nm), or blue (450 nm) wavelength for 30 days, and similar tests were performed as mentioned in experiment 2. While in experiment five, after 30 days of respective wavelength treatments, all animals were sampled for gene expression studies. Our results show that exposure to dLAN and LL affects the daily clock as reflected by altered melatonin secretion and locomotor activity, compromises the learning, memory, and cognitive ability, and alterations in the expression levels of transcripts in the hypothalamus, cortex, and thalamus. The effect is night light intensity dependent. Further, blue light at night has less drastic effects than green and red light. These results could be of the potential use of framing the policies for the use of light at night.

Lactoferrin for the postoperative management of term neonates after gastrointestinal surgery.

BACKGROUND: Neonates who have undergone gastrointestinal surgery are particularly susceptible to infectious complications in the postoperative period. This may be due in part to disruption of the integrity of the gut and its altered intestinal microflora. Lactoferrin is a whey protein found in milk and is an important innate mammalian defence mechanism. Lactoferrin has been reported to have antimicrobial and anti-inflammatory properties. It has also been reported to help establish a healthy gut microflora and aid in the intestinal immune system. Lactoferrin supplementation has been reported to decrease sepsis in preterm infants. There may be a role for lactoferrin to reduce the incidence of sepsis, thus reducing morbidity and mortality and improving enteral feeding in postoperative term neonates. OBJECTIVES: The primary objective of this review was to evaluate the efficacy of administering lactoferrin on the incidence of sepsis and mortality in term neonates after gastrointestinal surgery. The secondary objective was to assess the impact of administering lactoferrin on time to full enteral feeds, the intestinal microflora, duration of hospital stay, and mortality before discharge in the same population. SEARCH METHODS: The Cochrane Neonatal Information Specialist searched the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Embase Ovid, CINAHL, the WHO ICTRP and ClinicalTrials.gov trials registries. The date of the last search was February 2023. There were no restrictions to language, publication year or publication type. We checked references of potentially relevant studies and systematic reviews. SELECTION CRITERIA: We planned to include randomised controlled trials that studied infants born at 37 or more weeks of gestation who had one or more episodes of gastrointestinal surgery within 28 days of birth, and compared administration of lactoferrin with a placebo. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. We planned to use the GRADE approach to assess the certainty of evidence for each outcome. MAIN RESULTS: We identified no published randomised controlled studies that assessed the efficacy of lactoferrin for the postoperative management of term neonates following gastrointestinal surgery. AUTHORS' CONCLUSIONS: There is currently no evidence available from randomised controlled trials to show whether lactoferrin is effective or ineffective for the postoperative management of term neonates after gastrointestinal surgery. There is a need for randomised controlled trials to be performed to assess the role of lactoferrin in this setting.

Advanced Electrochemical Reamer (EC-Reamer) for Root Canal Treatment.

OBJECTIVE: According to the American Association of Endodontists (AAE), 22 million endodontic procedures have been performed annually. Root canal treatment is needed to prevent infection and restore function when a tooth is severely infected or decayed. This procedure is the only way to preserve the natural tooth and avoid artificial replacement (implant, denture, etc.). The current study aims to develop an electrochemical reamer (EC-Reamer or EC-R) that can help to disinfect the canal system and thus improve the success rate of root canal treatment. METHODS: The COMSOL Multiphysics software was utilized to simulate the experimental setup and confirm the current flow in the electrolyte. The benchtop experimental approach follows a specific electrochemical protocol, (i) open circuit potential to monitor the electrochemical stabilization and (ii) potentiostatic scan at -9.0 V as the treatment stage. Identification of feasible reference electrode (RE) and insulation material for the exploratory benchtop studies considered platinum (Pt) and gold (Au) wire as the REs and hot melt adhesive (HMA) and liquid tape as the insulation materials. The antimicrobial effects of EC-R were analysed using Enterococcus faecalis (E. faecalis). One-way ANOVA with the Tukey post hoc test and a significance level of P<0.05 is used to compare the groups with an experimental duration of 60 seconds. RESULTS: The findings showed that magnitude and current fluctuations created by Pt wire are promising when compared to Au wire, while Pt-HMA pair is chosen considering Pt's good electrochemical inertness and HMA's easy handling, availability, and non-hazardous features. The use of potentiostatic duration of 1 s and 3 s resulted in >99.99% E. faecalis reduction. Duration at 5 s and above resulted in a total bacterial kill. Statistical analysis confirmed a significant difference among the groups tested with commercial and custom-built potentiostats. CONCLUSION: The outcome provided preliminary data for developing an EC-R prototype to enhance the antimicrobial effect during root canal treatment potentially. (EEJ-2022-01-04).

Proportion of Infant Neurodevelopment Trials Reporting a Null Finding: A Systematic Review.

CONTEXT: Discovering new interventions to improve neurodevelopmental outcomes is a priority; however, clinical trials are challenging and methodological issues may impact the interpretation of intervention efficacy. OBJECTIVES: Characterize the proportion of infant neurodevelopment trials reporting a null finding and identify features that may contribute to a null result. DATA SOURCES: The Cochrane library, Medline, Embase, and CINAHL databases. STUDY SELECTION: Randomized controlled trials recruiting infants aged <6 months comparing any "infant-directed" intervention against standard care, placebo, or another intervention. Neurodevelopment assessed as the primary outcome between 12 months and 10 years of age using a defined list of tools. DATA EXTRACTION: Two reviewers independently extracted data and assessed quality of included studies. RESULTS: Of n = 1283 records screened, 21 studies (from 20 reports) were included. Of 18 superiority studies, >70% reported a null finding. Features were identified that may have contributed to the high proportion of null findings, including selection and timing of the primary outcome measure, anticipated effect size, sample size and power, and statistical analysis methodology and rigor. LIMITATIONS: Publication bias against null studies means the proportion of null findings is likely underestimated. Studies assessing neurodevelopment as a secondary or within a composite outcome were excluded. CONCLUSIONS: This review identified a high proportion of infant neurodevelopmental trials that produced a null finding and detected several methodological and design considerations which may have contributed. We make several recommendations for future trials, including more sophisticated approaches to trial design, outcome assessment, and analysis.

Expanding the phenotype of Bruck syndrome: Severe limb deformity, arthrogryposis, congenital cardiac disease and pulmonary hemorrhage.

Bruck syndrome is a rare collagen disorder with autosomal recessive inheritance caused by pathogenic variants in either FKBP10 or PLOD2 genes. It is characterized by bone fragility and fractures similar in severity and variability to osteogenesis-imperfecta as well as congenital joint contractures. This article describes an infant with a homozygous (partial) gene deletion of PLOD2 that includes the start codon and would be expected to lead to nonfunctional protein product. The infant had a severe phenotype of Bruck syndrome and is the only reported case of Bruck syndrome with congenital cardiac disease (triscuspid valve dysplasia with severe regurgitation, mitral valve prolapses with moderate regurgitation, and pulmonary hypertension) and pulmonary hemorrhage. We hypothesize that the additional feature of congenital cardiac disease in this case was due to the underlying defect in type I collagen, and that the pulmonary hemorrhage was multifactorial, with underlying vessel fragility, rib fractures, and high pulmonary pressures likely to be major contributing factors. Management was largely supportive with the use of bisphosphonates to assist in pain management. Care was complicated by comorbid cardiopulmonary compromise, limited evidence-base guiding care, and difficulties in discussing end-of-life care.

Growth and risk of adverse neuro-developmental outcome in infants with congenital heart disease: A systematic review.

AIM: Congenital heart disease (CHD) is one of the most common birth defects affecting around 1:100 infants. In this systematic review, we aimed to determine impact of growth on neurodevelopmental outcomes of infants with CHD. METHODS: Studies that reported association of growth with developmental outcomes in infants with CHD who had surgery, were included. The search strategy was prospectively registered. Relevant studies were identified by electronic searches. The Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE were searched from their earliest date to February 2022. RESULTS: Twenty studies met inclusion criteria. Choice of growth measures, developmental assessment tools and timing of assessment varied widely precluding conduct of a meta-analysis. Seventeen studies reported on infants who had cardio-pulmonary bypass. Birth weight was reported in thirteen studies and was associated with adverse outcome in nine. Head circumference at birth and later predicted developmental outcomes in five. Impaired postnatal growth was associated with adverse developmental outcome in seven studies. CONCLUSION: Growth in infants with congenital heart disease, specifically single ventricle physiology can predict adverse neurodevelopmental outcome. Included studies showed significant clinical heterogeneity. Uniformity should be agreed by various data registries with routine prospective collection of growth and developmental data.

Growth and risk of adverse neurodevelopmental outcome in infants with congenital surgical anomalies: a systematic review.

Survival of infants with congenital anomalies requiring surgical correction has increased dramatically, shifting the focus of clinical care and research toward optimising growth and neurodevelopment.To determine the impact of growth on neurodevelopmental outcomes of infants with congenital surgical anomalies. Studies that reported association of growth with developmental outcomes in infants with congenital anomalies who had surgery, were eligible for inclusion. The search strategy was prospectively drafted, and relevant studies were identified by electronic searches. The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2022, issue 1), MEDLINE and EMBASE from their earliest date to February 2022 were searched. Seven studies met the inclusion criteria. Variability in selection of growth measures, developmental assessment tools and assessment endpoints for neurodevelopment, precluded a meta-analysis. Four studies reported the association between growth and neurodevelopmental outcomes in infants with gastroschisis with two noting adverse outcomes in infants who were small for gestational age. Birthweight, reported in four studies, was not associated with adverse developmental outcomes. Postnatal growth, reported in three studies, was associated with adverse outcome. The data linking growth restriction in infants with congenital surgical anomalies and neurodevelopmental outcome is limited. There is limited published research examining the longitudinal effects of intra- and extra-uterine growth parameters on neurodevelopmental outcomes.

Changing indications and antenatal prognostic factors for ex-utero intrapartum treatment procedures.

OBJECTIVE: In cases of suspected neonatal airway obstruction, the ex-utero intrapartum treatment (EXIT) procedure is used to secure the airway while a fetus remains on placental circulation. We report indications and outcomes from all EXIT procedures at a tertiary obstetric unit between 1997 and 2020. METHOD: Retrospective cohort study with data collected from maternal and neonatal medical records. RESULTS: Indications for EXIT procedures were micrognathia (n = 7), lymphatic malformations (n = 5), cervical teratomas (n = 4), goiters (n = 2), and intra-oral epulis (n = 1). Infants with a fetal teratoma were delivered earliest due to 75% presenting with preterm premature rupture of membranes or preterm labor. Low birth weight was found in 75% of these neonates; they did not survive 1 year. Intubation at EXIT occurred for 58% (n = 11) of babies, and six neonates required a tracheostomy. In four cases of fetal micrognathia, the inferior facial angle (IFA) was noted to be <5th centile. All but one micrognathia case had polyhydramnios. Of the total cohort, 75% of neonates were alive at 1 year. CONCLUSION: Risks for neonatal demise with EXIT include fetal teratoma, low birth weight, and prematurity. Micrognathia has become an increasingly valid indication for the procedure. The combination of polyhydramnios and IFA <5% correlates well with severe airway obstruction and suggests consideration of EXIT.

D actylogyrus kolodynensis sp. n. (Platyhelminthes: Monogenea) infecting gills of Osteobrama cotio (Hamilton, 1822) (Cypriniformes: Cyprinidae) from India.

Dactylogyrus kolodynensis, a new monogenean parasite species, is described from Osteobrama cotio (Cyprinidae) collected from Lawngtlai (Mizoram) and Lucknow (Uttar Pradesh), India, using morphological examination and sequencing of partial 28S rRNA gene. The new species is morphologically characterized and distinguished from closely related congeners by a combination of the following characters: copulatory tube a loose coil of one complete clockwise ring, jaw-shaped accessory piece comprising variable sheathes enclosing and guiding the copulatory tube, and sclerotized vaginal tube, with a terminal flower-bud-shaped vaginal pore. The molecular analyses of specimens of D. kolodynensis collected from two different localities using 28S rRNA gene showed identical genotype that did not match any of the known sequences in GenBank, confirming our initial morphological identification. Dactylogyrus cotius, a sympatric species on the gills of O. cotio, is regarded as a species inquirenda because of its poor description. This is the first report of a monogenean species from Mizoram, in northeast India, bringing the total number of Dactylogyrus species in India to 57.

Seasonality in tropical birds.

The survival of offspring depends on environmental conditions. Many organisms have evolved with seasonality, characterized as initiation-termination-reinitiation of several physiological processes (i.e., body fattening, molt, plumage coloration, reproduction, etc). It is an adaptation for the survival of many species. Predominantly seasonal breeders use photoperiod as the most reliable environmental cue to adapt to seasonal changes but supplementary factors like temperature and food are synergistically involved in seasonal processes. Studies from diverse vertebrate systems have contributed to understanding the mechanism involved in seasonal reproduction at the molecular and endocrine levels. Long-day induced thyrotropin (thyroid-stimulating hormone) released from the pars tuberalis of the pituitary gland triggers local thyroid hormone activation within the mediobasal hypothalamus. This locally produced thyroid hormone, T3, regulates seasonal gonadotropin-releasing hormone secretion. Most of the bird species studied are seasonal in reproduction and linked behavior and, therefore, need to adjust reproductive decisions to environmental fluctuations. Reproductive strategies of the temperate zone breeders are well-documented, but less is known about tropical birds' reproduction and factors stimulating the annual breeding strategies. Here, we address seasonality in tropical birds with reference to seasonal reproduction and the various environmental factors influencing seasonal breeding.