Placental expression of miR-21-5p, miR-210-3p and miR-141-3p: relation to human fetoplacental growth.

BACKGROUND/OBJECTIVES: Dysregulation of microRNAs (miRNAs) and their target genes in placental tissue is associated with foetal growth restriction. We aimed to evaluate associations of placental miR-21-5p, miR-141-3p and miR-210-3p expression with maternal, placental and newborn parameters and with placental expression of their potential target genes PTEN, VEGF, FLT and ENG in a set of well-characterized small- (SGA) and appropriate- (AGA) for gestational age full-term singleton pregnancies. SUBJECTS/METHODS: Placental samples (n = 80) from 26 SGA and 54 AGA were collected from full-term singleton pregnancies. Placental transcript abundances of miR-21-5p, miR-141-3p and miR-210-3p were assessed after normalization to a reference miRNA, mir-16-5p by real-time quantitative PCR. Placental transcript abundances of PTEN, VEGF, FLT and ENG were assessed after normalizing to a panel of reference genes. RESULTS: Placental miR-21-5p transcript abundance was negatively associated with placental weight (n = 80, r = -0.222, P = 0.047) and this association was specific to the AGA births (n = 54, r = -0.292, P = 0.032). Placental transcript abundances of miR-210-3p and miR-141-3p were not associated with placental weight or birth weight in all 80 births. However, placental miR-210-3p transcript abundance was positively associated with birth weight specifically in the SGA births (n = 26, r = 0.449, P = 0.021). Placental transcript abundance of miR-21-5p was negatively associated with PTEN transcript abundance (Spearman's ρ = -0.245, P = 0.028) while that of miR-141-3p was positively associated with FLT (Spearman's ρ = 0.261, P = 0.019) and ENG (Spearman's ρ = 0.259, P = 0.020) transcript abundances in all 80 births. CONCLUSION: We conclude that placental miR-21-5p and miR-210-3p may be involved in fetoplacental growth. However, this regulation is unlikely to be mediated through placental expression of PTEN, VEGF, FLT or ENG.

Placental expression of RNU44, RNU48 and miR-16-5p: stability and relations with fetoplacental growth.

BACKGROUND/OBJECTIVES: The current study aimed to identify suitable reference miRNA for placental miRNA expression analysis in a set of well-characterized and fetal-sex balanced small- (SGA) and appropriate- (AGA) for gestational age full-term singleton pregnancies. SUBJECTS/METHODS: In this retrospective study, placental samples (n = 106) from 35 SGA (19 male and 16 female) and 71 AGA (30 male and 41 female) full-term singleton pregnancies were utilized. Placental transcript abundance of three widely used reference miRNAs [miR-16-5p and Small nucleolar RNAs (snoRNAs) RNU44 and RNU48] were assessed by real-time quantitative PCR. Raw cycle threshold (Ct) analysis and RefFinder tool analysis were conducted for evaluating stability of expression of these miRNAs. RESULTS: Raw Ct values of miR-16-5p were similar between SGA and AGA births (P = 0.140) and between male and female births within SGA (P = 0.159) and AGA (P = 0.060) births while that of RNU44 and RNU48 were higher in SGA births (P = 0.008 and 0.006 respectively) and in male births within the SGA group (P = 0.005) for RNU44 and in female births within the AGA group (P = 0.048) for RNU48. Across all 106 samples tested using the RefFinder tool, miR-16-5p and RNU44 were equally stable reference miRNAs. CONCLUSION: We recommend miR-16-5p and RNU44 as suitable reference miRNAs for placental samples from settings similar to our study.

microRNA signatures associated with fetal growth restriction: a systematic review.

Placental-origin microRNA (miRNA) profiles can be useful toward early diagnosis and management of fetal growth restriction (FGR) and associated complications. We conducted a systematic review to identify case-control studies that have examined miRNA signatures associated with human FGR. We systematically searched PubMed and ScienceDirect databases for relevant articles and manually searched reference lists of the relevant articles till May 18th, 2021. Of the 2133 studies identified, 21 were included. FGR-associated upregulation of miR-210 and miR-424 and downregulation of a placenta-specific miRNA cluster miRNA located on C19MC (miR-518b, miR-519d) and miR-221-3p was reported by >1 included studies. Analysis of the target genes of these miRNA as well as pathway analysis pointed to the involvement of angiogenesis and growth signaling pathways, such as the phosphatidylinositol 3-kinase- protein kinase B (PI3K-Akt) pathway. Only 3 out of the 21 included studies reported FGR-associated miRNAs in matched placental and maternal blood samples. We conclude that FGR-associated placental miRNAs could be utilized to inform clinical practice towards early diagnosis of FGR, provided enough evidence from studies on matched placental and maternal blood samples become available.Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42019136762.

Placental expression of leptin: fetal sex-independent relation with human placental growth.

OBJECTIVES: Leptin (LEP) is a vital placental hormone that is known to affect different aspects of placental function and fetal development. The present study aimed to determine the association of placental LEP transcript abundance with maternal, placental, and newborn parameters. SUBJECTS/METHODS: In this retrospective case-control study, placental samples (n = 105) were collected from small (SGA) and appropriate (AGA) for gestational age full-term singleton pregnancies (n = 44 SGA and n = 61 AGA). Placental transcript abundance of LEP was assessed by real-time quantitative PCR after normalization to a reference gene panel. LEP methylation was measured using a quantitative MethyLight assay in a subset of samples (n = 54). RESULTS: Placental LEP transcript abundance was negatively and significantly associated with placental weight (ß = -3.883, P = 0.015). This association continued to be significant in the SGA group (ß = -10.332, P = 0.001), both in female (ß = -15.423, P = 0.021) and male births (ß = -10.029, P = 0.007). LEP transcript abundance was not associated with LEP methylation levels (Spearman's ρ = 0.148, P = 0.287). CONCLUSION: We conclude that placental upregulation of LEP is an integral and fetal sex-independent component of placental growth restriction, which can be potentially targeted through maternal dietary modifications to improve fetoplacental growth.

Placental expression of ENG, VEGF, and FLT: Gender-specific associations with maternal vitamin B12 status.

OBJECTIVES: Adequate vitamin B12 is a requisite during pregnancy and its deficiency is linked with increased risk for adverse outcomes, likely mediated by impaired placental angiogenesis. Thus, we aimed to test associations of maternal vitamin B12 status with the placental expression of angiogenesis-associated genes ENG, VEGF, and FLT. SUBJECTS/METHODS: In this retrospective case-control study, placental and maternal trimester 1 blood samples (n = 104) were collected from small for gestational age (SGA) and appropriate for gestational age (AGA) full-term singleton pregnancies. Maternal trimester 1 vitamin B12 status was measured. Placentae and neonates were weighed at birth. Realtime quantitative PCR was performed to assess placental transcript abundance of ENG, VEGF, and FLT normalized to a panel of reference genes. Associations of placental transcript abundance of the genes with maternal trimester 1 vitamin B12 status were evaluated. RESULTS: Placental ENG transcript abundance associated negatively with maternal trimester 1 vitamin B12 status (ß = -0.461, P = 0.017, n = 104). This association was specific to the female births (ß = -0.590, P = 0.014, n = 60). Placental VEGF transcript levels were negatively associated with maternal trimester 1 vitamin B12 status only in the female births (ß = -1.995, P = 0.029). Placental FLT transcript levels were not associated with maternal trimester 1 vitamin B12 status. CONCLUSION: Maternal trimester 1 vitamin B12 status was associated negatively with placental ENG and VEGF expression predominantly in the female births. Therefore, we hypothesize that the placenta adapts to low maternal vitamin B12 status by up-regulating angiogenic pathways in a gender-specific manner.

Visual inspection of cervix with Lugol's iodine for early detection of premalignant & malignant lesions of cervix.

BACKGROUND & OBJECTIVES: Majority of cases of cervical cancer are diagnosed at an advanced stage as cytology based screening programmes are ineffective in developing countries. The present study was done to look for carcinoma cervix and its precursors by visual inspection with Lugol's iodine (VILI), visual inspection with acetic acid (VIA) and Papanicolaou smear, and to analyse their sensitivity, specificity and predictive values using colposcopic directed biopsy as reference. METHODS: In this cross-sectional study, 350 women were subjected to Pap smear, VIA, VILI and colposcopy. Cervical biopsy and endocervical curettage was taken from patients positive on any of these tests and in 10 per cent of negative cases. RESULTS: The Pap smear was abnormal in 3.71 per cent, including (2.85%), low grade (LSIL) and (0.85%) high grade squamous intraepithelial lesions (HSIL). Thirteen per cent of the patients were found to be positive by VIA and 11.71 per cent were positive on VILI. Sensitivity for VIA, VILI and Pap smear was 89.5, 100 and 52.6 per cent, respectively, while the specificity for VIA, VILI and Pap smear was 91.2, 93.3 and 99.1 per cent, respectively. INTERPRETATION & CONCLUSIONS: In low resource settings, cervical cancer screening by Pap smear can be replaced by visual methods like VILI, which has the highest sensitivity (100%) to detect any grade of dysplasia, and a good specificity (93.3%).

Autistic spectrum disorder traits in children with attention deficit hyperactivity disorder.

BACKGROUND: Current classification systems do not allow for comorbid diagnoses of attention deficit hyperactivity disorder (ADHD) and autistic spectrum disorder (ASD). Children with ADHD are often screened for ASD during clinical assessment and when recruited to clinical trials. We predicted that children with ADHD would have more autistic traits than controls and that certain traits would be more prevalent. METHODS: The clinically referred sample consisted of 30 children with ADHD and 30 matched controls aged 9-15 years. Children were screened for ASD traits using the Social Aptitudes Scale (SAS) and the Social Communication Questionnaire (SCQ). RESULTS: We found that ASD traits were significantly higher in children with ADHD than controls. None of the children received a diagnosis of autism or ASD. However, a large proportion (28% using the SCQ and 62% using the SAS) of children with ADHD reached screening thresholds for a predictive diagnosis of ASD. Relative to controls, children with ADHD had significantly higher levels of communication and social deficits, but not repetitive behaviours. CONCLUSION: Further work is needed to establish whether autistic-like communication and social difficulties in children with ADHD are part of the broader ASD phenotype or are specific to ADHD.

Translation and validation of brief patient health questionnaire against DSM IV as a tool to diagnose major depressive disorder in Indian patients.

CONTEXT: Depression is frequently encountered in the primary care setting but is often unrecognized and hence untreated. There is a need for a uniform user-friendly screening instrument for depression for primary healthcare personnel in India. AIMS: Translation and validation of the brief patient health questionnaire (BPHQ) as a screening tool for depression in major Indian languages. MATERIALS AND METHODS: This was a prospective study conducted at 18 sites, in psychiatric and general clinics. The English version of the BPHQ was translated into 11 Indian languages. The translations were reviewed by experts and volunteers and proofread for the final translated BPHQ. The validation exercise included more than 3000 subjects. A psychiatrist and a psychiatry social worker / coordinator conducted the study under the supervision of the principal investigator. For each language, the presence or absence of major depressive disorder (MDD) as diagnosed with the help of a patient-completed BPHQ and the psychiatrist DSM-IV diagnosis was matched. The kappa coefficient was used as a measure of inter-observer agreement between the two diagnostic methods. RESULTS: Seven languages failed the primary validation exercise. These translations were reviewed and the updated versions, after proofreading were re-run for validation. The self-administered BPHQ was successfully translated and validated for diagnosis of MDD against DSM-IV diagnosis made by a psychiatrist, in English, Hindi, Marathi oriya, Malayalam, Assamese, Gujarati, Kannada, Telugu, Bengali and Tamil. CONCLUSIONS: BPHQ is a simple, quick and reliable instrument, which facilitates rapid and accurate diagnosis of depression in the primary care setting in our country.

Guideline for the management of pediatric idiopathic constipation and soiling. Multidisciplinary team from the University of Michigan Medical Center in Ann Arbor.

OBJECTIVE: To develop an evidence-based guideline for the primary pediatric care of children (birth to 18 years old) with idiopathic constipation and soiling. DATA SOURCES: References were identified through a MEDLINE search from January 1975 through January 1998 to address 3 focus questions: (1) the best path to early, accurate diagnosis; (2) best methods for adequate clean-out; and (3) best approaches to promote patient and family compliance with management. DATA SELECTION: Twenty-five references were identified. DATA EXTRACTION: References were reviewed by a multidisciplinary team and graded according to the following criteria: randomized controlled trial; controlled trial, no randomization; observational study; and expert opinion. Evidence tables were developed for each focus question. DATA SYNTHESIS: An algorithm and clinical care guideline were developed by consultation and consensus among team members. Emphasis was placed on methods to promote early identification of pediatric idiopathic constipation and soiling, to recognize points of referral, and to increase patient and family compliance with treatment through use of education, developmentally based interventions, and variables for tracking success of management. CONCLUSION: An algorithm and guideline for pediatric idiopathic constipation and soiling are presented for use by primary care physicians.

Improving vision: neural compensation for optical defocus.

Anecdotal reports abound of vision improving in myopia after a period of time without refractive correction. We explored whether this effect is due to an increased tolerance of blur or whether it reflects a genuine improvement in vision. Our results clearly demonstrated a marked improvement in the ability to detect and recognize letters following prolonged exposure to optical defocus. We ensured that ophthalmic change did not occur, and thus the phenomenon must be due to a neural compensation for the defocus condition. A second set of experiments measured contrast sensitivity and found a decrease in sensitivity to mid-range (5-25 cycles deg-1) spatial frequencies following exposure to optical defocus. The results of the two experiments may be explained by the unmasking of low contrast, high spatial frequency information via a two-stage process: (1) the pattern of relative channel outputs is maintained during optical defocus by the depression of mid-range spatial frequency channels; (2) channel outputs are pooled prior to the production of the final percept. The second set of experiments also provided some evidence of inter-ocular transfer, indicating that the adaptation process is occurring at binocular sites in the cortex.

Effect of chronic continuous positive airway pressure (CPAP) therapy on upper airway size in patients with sleep apnoea/hypopnoea syndrome.

BACKGROUND: There is evidence to suggest that chronic continuous positive airway pressure (CPAP) therapy may produce reversible changes in upper airway morphology and function in patients with sleep apnoea/hypopnoea. This study was designed to examine the effect of chronic CPAP therapy on upper airway calibre. METHODS: Twenty four men with the sleep apnoea/hypopnoea syndrome (mean (SE) apnoea/hypopnoea index 37 (5)) underwent lateral cephalometry with measurement of posterior airway space performed before and at least three months after initiation of CPAP therapy. RESULTS: There was no weight change between the two assessments and mean CPAP use was 4.8 (0.4) hours per night. Posterior airway space (PAS) was measured in erect and supine postures. PAS supine increased with CPAP therapy from a mean (SE) of 11.8 (0.8) mm to 13.4 (0.8) mm, but PAS erect did not. Correlation of the change in PAS (dPAS) before and after CPAP therapy showed an increase with increasing CPAP compliance measured as machine run time both for dPAS supine (r = 0.68) and dPAS erect (r = 0.47). CONCLUSIONS: Patients with the sleep apnoea/hypopnoea syndrome regularly using CPAP for more than four hours per night all showed an increase in dPAS supine. The use of chronic CPAP increases PAS supine probably by a reduction in upper airway oedema, and the change in size is dependent on CPAP use.