STRIDER NZAus: a multicentre randomised controlled trial of sildenafil therapy in early-onset fetal growth restriction.

OBJECTIVE: To assess the effect of maternal sildenafil therapy on fetal growth in pregnancies with early-onset fetal growth restriction. DESIGN: A randomised placebo-controlled trial. SETTING: Thirteen maternal-fetal medicine units across New Zealand and Australia. POPULATION: Women with singleton pregnancies affected by fetal growth restriction at 22+0 to 29+6 weeks. METHODS: Women were randomised to oral administration of 25 mg sildenafil citrate or visually matching placebo three times daily until 32+0 weeks, birth or fetal death (whichever occurred first). MAIN OUTCOME MEASURES: The primary outcome was the proportion of pregnancies with an increase in fetal growth velocity. Secondary outcomes included live birth, survival to hospital discharge free of major neonatal morbidity and pre-eclampsia. RESULTS: Sildenafil did not affect the proportion of pregnancies with an increase in fetal growth velocity; 32/61 (52.5%) sildenafil-treated, 39/57 (68.4%) placebo-treated [adjusted odds ratio (OR) 0.49, 95% CI 0.23-1.05] and had no effect on abdominal circumference Z-scores (P = 0.61). Sildenafil use was associated with a lower mean uterine artery pulsatility index after 48 hours of treatment (1.56 versus 1.81; P = 0.02). The live birth rate was 56/63 (88.9%) for sildenafil-treated and 47/59 (79.7%) for placebo-treated (adjusted OR 2.50, 95% CI 0.80-7.79); survival to hospital discharge free of major neonatal morbidity was 42/63 (66.7%) for sildenafil-treated and 33/59 (55.9%) for placebo-treated (adjusted OR 1.93, 95% CI 0.84-4.45); and new-onset pre-eclampsia was 9/51 (17.7%) for sildenafil-treated and 14/55 (25.5%) for placebo-treated (OR 0.67, 95% CI 0.26-1.75). CONCLUSIONS: Maternal sildenafil use had no effect on fetal growth velocity. Prospectively planned meta-analyses will determine whether sildenafil exerts other effects on maternal and fetal/neonatal wellbeing. TWEETABLE ABSTRACT: Maternal sildenafil use has no beneficial effect on growth in early-onset FGR, but also no evidence of harm.

Role of secretin peptide family and their receptors in the hypothalamic control of energy homeostasis.

Secretin family of peptide hormones is a group of structurally related brain-gut peptides that exert their functions via interactions with the class B1 G protein-coupled receptors (GPCRs). Recent researches of these peptides and receptors in metabolism have been an area of intense focus for the development of promising drug targets as therapeutic potentials for metabolic disorders. The fact that agonists of GLP-1, a member in the family, have already started being used as therapeutics clearly indicates the importance and relevance of further research on the clinical applications of these peptides. This review aims to provide an overview of the current understanding regarding the importance of this family of peptides as well as their receptors in metabolism with special focus on their actions in the hypothalamus.

Bibliometric analysis of research on dental age estimation.

Dental age estimation plays a key role in therapeutic, medicolegal, forensic, and anthropological applications. The purpose of this study is to evaluate the research progress on dental age estimation using bibliometric analysis. Data were gathered from Scopus, Web of Science and PubMed. Keyword co-occurrence analysis, collaboration network analysis, and descriptive analysis of bibliographic data were all completed using VOS viewer and Biblioshiny software. There has been an ongoing but gradual rise in research regarding dental age estimation, with notable increase since 2014. The country with the most publications published (205) was India. The year of 2018 (TP = 92) and 2021 (TP = 100) saw a rapid spike in publications and citations, respectively. The Shanghai Jiao Tong University School of Medicine, which has 153 citations, was the most productive institution. Forensic Science International was the journal with the greatest number of publications (73). Author Cameriere had the maximum number of publications (30). The increase in publications associated to collaboration across numerous authors, nations, and institutes serves as evidence of the significant improvement in dental age estimation. This citation analysis allows for the identification of the most relevant and pertinent research fields while providing a view on the development of research in the field of dental age estimation.

Bacterial water quality and network hydraulic characteristics: a field study of a small, looped water distribution system using culture-independent molecular methods.

AIMS: To determine the spatial and temporal variability in the abundance, structure and composition of planktonic bacterial assemblages sampled from a small, looped water distribution system and to interpret results with respect to hydraulic conditions. METHODS AND RESULTS: Water samples were collected from five sampling points, twice a day at 06:00 h and 09:00 h on a Monday (following low weekend demand) and a Wednesday (higher midweek demand). All samples were fully compliant with current regulated parameter standards. This study did not show obvious changes in bacterial abundance (DAPI count) or community structure Denaturing gradient gel electrophoresis analysis with respect to sample site and hence to water age; however, the study did show temporal variability with respect to both sampling day and sample times. CONCLUSIONS: Data suggests that variations in the bacterial assemblages may be associated with the local system hydraulics: the bacterial composition and numbers, over short durations, are governed by the interaction of the bulk water and the biofilm influenced by the hydraulic conditions. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates general stability in bacterial abundance, community structure and composition within the system studied. Trends and patterns supporting the transfer of idealized understanding to the real world were evident. Ultimately, such work will help to safeguard potable water quality, fundamental to public health.

Transcatheter closure of a residual aortopulmonary window through internal jugular vein access.

The use of Amplatzer septal occluder for closing a residual aortopulmonary defect has been described. This is usually performed by femoral access. We report closure of a residual aortopulmonary defect using right internal jugular vein access in a patient who had no femoral access as a result of previous cannulation for surgical repair. The 1 cm defect was closed successfully using a 10 mm Amplatzer septal occluder. Technical difficulty anticipated was unfounded although it was more cumbersome than femoral access. Left to right cardiac defects including PDA and AP window are amenable to transcatheter closure through internal jugular vein access.

A novel, cost-effective lens irrigation system for rigid endoscopes in transnasal endoscopic surgery.

BACKGROUND: In transnasal endoscopic surgical procedures, the lens of the endoscope often becomes fogged or smeared with mucus or blood. The surgeon has to clean the lens and reintroduce the endoscope multiple times during the surgery, making it a tiring process. METHODS: This paper describes an innovative lens irrigation system comprising a modified 16 Fr Foley catheter, a 20 cc or 50 cc syringe filled with warm normal saline (0.9 per cent), and a commercially available intravenous infusion set. The rigid endoscope is introduced into the catheter through the urine draining port. When the lens gets smudged with blood or mucus, the irrigating saline in the syringe is forced through the inflating port. RESULTS: A clear vision was restored immediately on flushing the syringe. The system did not compromise the operative space or hinder manoeuvrability. CONCLUSION: This cost-effective, innovative lens irrigation system saves the time spent in cleaning the lens and enhances operational efficiency, especially in a low-income setting.

Increasing body mass index and abdominal subcutaneous fat thickness are associated with increased skin-to-epidural space distance in pregnant women.

BACKGROUND: Body mass index does not indicate the distribution of adipose tissue. Central adiposity may be measured using ultrasound measurement of subcutaneous fat thickness. This study determined if the abdominal subcutaneous fat thickness measured correlated with skin-to-epidural space distance at delivery, and compared this with the booking body mass index. METHODS: We analysed a sub-set of participants from a single-centre, prospective cohort study that assessed the relationship between subcutaneous fat thickness and maternity outcomes. Abdominal subcutaneous fat thickness measurements were obtained during the routine fetal anomaly scan. The skin-to-epidural space distance was obtained in those having epidural or combined spinal-epidural analgesia. Linear regression was used to test for strength of association and adjusted R2 values calculated to determine if subcutaneous fat thickness or body mass index was more strongly associated with skin-to-epidural space distance. RESULTS: The 463 women had a median (IQR) booking body mass index of 25.0 kg/m2 (21.8-29.3) and subcutaneous fat thickness of 16.2 mm (13.0-21.0). The median (IQR) skin-to-epidural space distance was 5.0 cm (4.5-6.0). Both parameters significantly correlated with skin-to-epidural space distance (r=0.53 and 0.68 respectively, P <0.001). Adjusted linear regression coefficient (95% CI) for subcutaneous fat thickness was 0.09 (0.08 to 0.11), R2=0.30 and for body mass index 0.12 (0.11 to 0.13), R2=0.47. CONCLUSIONS: Booking body mass index had a stronger relationship with skin-to- epidural space distance at delivery than subcutaneous fat thickness, explaining 47% of the variation in the skin-to-epidural distance.

Method development and validation for the simultaneous determination of cetirizine dihydrochloride, paracetamol, and phenylpropanolamine hydrochloride in tablets by capillary zone electrophoresis.

A simple, selective, and cost effective capillary zone electrophoresis (CZE) method has been developed for the simultaneous separation and determination of cetirizine dihydrochloride (CTZ), paracetamol (PARA), and phenylpropanolamine hydrochloride (PPA) in tablets. A 10 mM sodium tetraborate background electrolyte (BGE) solution (pH 9.0) was found to be suitable for separation of all the analytes. An uncoated fused-silica capillary of a total length of 76 cm (effective length 64.5 cm) was used for separation. All the analytes were completely separated within 10 min at the applied voltage of 20 kV (current produced approximately 21 microA), and detection was performed at 195 nm with an UV detector. Ibuprofen was used as internal standard (I.S.) for the quantification of the drugs. Validation of the method was performed in terms of linearity, accuracy, precision, limit of detection (LOD), and quantification (LOQ). The linearity of the calibration curves for CTZ, PARA, and PPA (tested range) were 2-50 microg ml(-1) (r(2)=0.9982), 10-1000 microg ml(-1) (r(2)=0.9978), and 10-100 microg ml(-1) (r(2)=0.9986), respectively. The proposed method has been applied for the determination of active ingredients in tablets, and the recovery was found to be > or =98.60% with the relative standard deviation (R.S.D.) < or =1.56%. The LOQ of the CTZ, PARA, and PPA was found to be 2.0, 2.0, and 4.0 microg ml(-1), respectively. There were no interfering peaks due to the excipients present in the pharmaceutical tablets. Thus, the proposed method is simple and suitable for the simultaneous analysis of active ingredients in tablet dosage forms.

Pharmacological Actions of Glucagon-Like Peptide-1, Gastric Inhibitory Polypeptide, and Glucagon.

Glucagon family of peptide hormones is a group of structurally related brain-gut peptides that exert their pleiotropic actions through interactions with unique members of class B1 G protein-coupled receptors (GPCRs). They are key regulators of hormonal homeostasis and are important drug targets for metabolic disorders such as type-2 diabetes mellitus (T2DM), obesity, and dysregulations of the nervous systems such as migraine, anxiety, depression, neurodegeneration, psychiatric disorders, and cardiovascular diseases. The current review aims to provide a detailed overview of the current understanding of the pharmacological actions and therapeutic advances of three members within this family including glucagon-like peptide-1 (GLP-1), gastric inhibitory polypeptide (GIP), and glucagon.

Simultaneous determination of HIV-protease inhibitors lamivudine and zidovudine in pharmaceutical formulations by micellar electrokinetic chromatography.

A micellar electrokinetic chromatographic (MEKC) method for the simultaneous separation and determination of lamivudine (LMV) and zidovudine (ZDV) in pharmaceutical formulation has been developed. Factors that affect the separation, such as buffer pH, surfactant concentration (sodium dodecyl sulfate, SDS), organic solvents and applied voltage were optimized. Buffer consisting of 12.5 mM sodium tetraborate decahydrate and 15 mM boric acid adjusted at pH 10.8, containing 90 mM SDS and 5% (v/v) acetonitrile (ACN) was found to be suitable for the separation of the drugs. p-Aminobenzoic acid (PABA) was used as internal standard (I.S.). Detection of analytes and I.S. was performed at a wavelength of 210 nm. It was observed that both the drugs and I.S. were migrated within 20 min at the applied voltage of +10 kV. Validation of the method was performed in terms of linearity, accuracy, precision, limit of detection (LOD) and quantification (LOQ). An excellent linearity was obtained in the concentration range 10-80 microg/ml for LMV and 10-100 microg/ml for ZDV. The detection limits for LMV and ZDV were found to be 2.5 and 2.0 microg/ml, respectively. The optimized method was applied to the simultaneous determination of LMV and ZDV in pharmaceutical formulation and human plasma (spiked) samples. Recovery of both the drugs in tablet dosage form and spiked drugs in plasma were > or =99.72% (relative standard deviation (R.S.D.)< or =1.84%) and > or =80.4% (R.S.D.< or =5.4%), respectively. In the electropherogram no interfering peaks were observed in the region of analytes and I.S. due to inactive ingredients in the tablets and matrices in plasma.

Enantiomeric separation and determination of antiparkinsonian drugs by reversed-phase ligand-exchange high-performance liquid chromatography.

A simple and rapid high-performance liquid chromatographic method for the separation and determination of enantiomers of levodopa and carbidopa using a LiChrosper C18 column with aqueous copper-L-phenylalanine as mobile phase was developed. The separation between D- and L-enantiomers of levodopa and carbidopa was fairly good with separation factors of 1.63 and 2.38, respectively. The method was validated using synthetic mixtures and used for quality assurance of commercial formulations.

Indirect photometric assay determination of gabapentin in bulk drug and capsules by capillary electrophoresis.

A capillary electrophoresis (CE) method was developed for the assay determination of gabapentin (GBP) in bulk drug and capsules. Separation was carried out on 74cm (62.5cm effective length) x 75microm i.d. fused silica capillary by applying a potential of -20kV at ambient temperature. Background electrolyte (BGE) consisting of 5mM 5-sulphosalicylic acid and 0.5mM cetyltrimethylammonium bromide (CTAB), pH 11.0 was employed for the separation. Indirect method of UV detection was performed at a wavelength of 215nm using sulphosalicylate ion as a chromophore. A linear calibration curve was obtained over a concentration range 20-200microg/ml of GBP in deionized water with a correlation coefficient (r) of 0.9998. Recoveries were shown to be >/=98% both in bulk drug and capsules with standard deviation (S.D.)

Development and validation of an analytical method for the separation and determination of major bioactive curcuminoids in Curcuma longa rhizomes and herbal products using non-aqueous capillary electrophoresis.

A simple, fast and efficient non-aqueous capillary electrophoresis method (NACE) was developed for the simultaneous determination of three major bioactive curcuminoids (CMNs) in Curcuma longa rhizomes and its herbal products. Good separation, resolution and reproducibility were achieved with the background electrolyte (BGE) consisting a mixture of 15.0 mM sodium tetraborate and 7.4 mM sodium hydroxide (NaOH) in 2:10:15 (v/v/v) of water, 1-propanol, and methanol. The influences of background electrolyte, sodium hydroxide, water, sodium dodecyl sulfate and hydroxylpropyl-ß-cyclodextrin on separations were investigated. The separation was carried out in a fused-silica capillary tube with reverse polarity. Hydrodynamic injection of 25mbar for 12s was used for injecting samples and a voltage of 28 kV was applied for separation. The ultrasonication method was used for the extraction of CMNs from the turmeric herbal products and the extract was filtered and directly injected without any further treatments. The limits of detection and quantification were less than 5.0 and 14.6 µg/ml respectively for all CMNs. The percentage recoveries for CMNs were >97.2% (%RSD, <2.62). The results obtained by the method were compared with existing spectrophotometric and HPLC methods. The related compounds in the extract did not interfere in the determination of CMNs. The proposed NACE method is better than existing chromatographic and electrophoretic methods in terms of simple electrophoretic medium, fast analysis and good resolution.