Tranexamic acid, as an adjunct to oxytocin prophylaxis, in the prevention of postpartum haemorrhage in women undergoing elective caesarean section: A single-centre double-blind randomised controlled trial.

OBJECTIVE: To evaluate the effectiveness of tranexamic acid (TXA) in reducing blood loss during elective caesarean sections in women with and without risk factors for postpartum haemorrhage (PPH). DESIGN: A double-blind, randomised placebo-controlled trial. SETTING: An academic tertiary referral centre in Singapore. POPULATION: Multiethnic women aged 21 years or older undergoing elective caesarean section. METHODS: Randomisation to intravenous TXA or normal saline (placebo) 10 minutes before skin incision. MAIN OUTCOME MEASURES: Calculated estimated blood loss (cEBL), derived from blood volume and haematocrit levels. RESULTS: Between June 2020 and October 2021, 200 women were randomised to the placebo or TXA groups. Women who received prophylactic TXA had a significantly lower mean cEBL compared with those receiving placebo (adjusted mean difference -126.4 mL, 95% CI -243.7 to -9.1, p = 0.035). The effect was greatest in those at high risk for PPH, with a reduction in cEBL (mean difference -279.6 mL, 95% CI -454.8 to -104.3, p = 0.002) and a lower risk of cEBL ≥500 mL (risk ratio [RR] 0.54, 95% CI 0.36-0.83, p = 0.007) and cEBL ≥1000 mL (RR 0.44, 95% CI 0.20-0.98, p = 0.016). Subgroup analysis showed benefit for women with preoperative haemoglobin <10.5 g/dL (mean difference -281.9 mL, 95% CI -515.0 to -48.8, p = 0.019). There was no significant difference in need for additional medical or surgical interventions. There were no maternal or neonatal adverse outcomes. CONCLUSION: Prophylactic TXA should be considered in women with risk factors for PPH, and those most likely to benefit are those with preoperative haemoglobin <10.5 g/dL.

Hyperandrogenism, Insulin Resistance, and Acanthosis Nigricans (HAIR-AN) Syndrome Reflects Adipose Tissue Dysfunction ("Adiposopathy" or "Sick Fat") in Asian Indian Girls.

BACKGROUND: Whether HAIR-AN syndrome and polycystic ovarian syndrome (PCOS) are distinct entities or represent a phenotypic spectrum of the same syndrome is still unclear. HAIR-AN syndrome is characterized by high insulin resistance, obesity, and hyperinsulinemia as compared to PCOS and could represent adipose tissue dysfunction as the primary pathophysiologic trigger. This study was undertaken to study the role of adipose tissue dysfunction in HAIR-AN syndrome and PCOS using adipocytokines as surrogate markers of "adiposopathy." MATERIALS AND METHODS: A cross-sectional observational study was conducted at a tertiary care hospital over a period of 1 year. Serum adiponectin, leptin, IL-6, and TNF-α levels were measured in 30 women with HAIR-AN syndrome and in 30 women with PCOS. Correlations between adipocytokines, inflammatory markers, serum testosterone, and serum insulin were determined. Data analysis was performed using the SPSS version 23.0 (IBM SPSS Statistics Inc., Chicago, IL, USA) software program. RESULTS: Women with HAIR-AN syndrome had significantly higher hyperandrogenemia, hyperinsulinemia, and insulin resistance as compared to PCOS women. They also had high leptin levels and lower adiponectin levels (p < 0.001). However, the levels of inflammatory markers (TNF-α and IL-6) were similar in both the groups (p > 0.05). Serum adiponectin showed a negative correlation with HOMA-IR and testosterone levels, while leptin showed a positive correlation with both in HAIR-AN patients while no such correlation was found in the PCOS group. CONCLUSION: The significantly raised adipocytokines in HAIR-AN syndrome patients as compared to PCOS patients indicates the primary role of adipose tissue dysfunction ("adiposopathy") in the pathogenesis of HAIR-AN syndrome while only a minor role, if any, in PCOS. Both these syndromes stand as distinct entities pathogenically with an overlapping phenotype.

Thermal Energy Electrons and OH-Radicals Induce Strand Breaks in DNA in an Aqueous Environment: Some Salts Offer Protection Against Strand Breaks.

Electrons and •OH-radicals have been generated by using low-energy laser pulses of 6 ns duration (1064 nm wavelength) to create plasma in a suspension of plasmid DNA (pUC19) in water. Upon thermalization, these particles induce single and double strand breakages in DNA along with possible base oxidation/base degradation. The time-evolution of the ensuing structural modifications has been measured; damage to DNA is seen to occur within 30 s of laser irradiation. The time-evolution is also measured upon addition of physiologically relevant concentrations of salts containing monovalent, divalent, or trivalent alkali ions. It is shown that some alkali ions can significantly inhibit strand breakages while some do not. The inhibition is due to electrostatic shielding of DNA, but significantly, the extent of such shielding is seen to depend on how each alkali ion binds to DNA. Results of experiments on strand breakages induced by thermalized particles produced upon plasma-induced photolysis of water, and their inhibition, suggest implications beyond studies of DNA; they open new vistas for utilizing simple nanosecond lasers to explore the effect of ultralow energy radiation on living matter under physiologically relevant conditions.

Minireview: Laser-Induced Formation of Microbubbles-Biomedical Implications.

Recent work is summarized that shows how microbubbles may have potential utility in biomedical situations as (i) highly localized generators of intense white light in an aqueous environment, (ii) disruptors of matter in aqueous solution, (iii) essential precursors in laser-writing structures on substrates on which biological cells can be spatially aligned, and (iv) mediators in the fabrication of hierarchical nanostructures that enhance signals in biological Raman spectroscopy. Indeed, microbubbles generated upon laser irradiation of surfaces have many more ramifications than originally thought, with implications in the laser modification of surfaces producing either hydrophilicity or hydrophobicity. Many more possibilities remain to be explored and exploited.

Strong Strand Breaks in DNA Induced by Thermal Energy Particles and Their Electrostatic Inhibition by Na+ Nanostructures.

Low-power laser pulses of 6 ns duration (1064 nm wavelength) have been used to create plasma in an aqueous solution of plasmid DNA (pUC19). Thermal energy electrons and •OH radicals in the plasma induce strand breakages in DNA, including double strand breaks and possible base oxidation/base degradation. The time evolution of these modifications shows that it takes barely 30 s for damage to DNA to occur. Addition of physiologically relevant concentrations of a salt (NaCl) significantly inhibits such damage. We rationalize such inhibition using simple electrostatic considerations. The observation that DNA damage is induced by plasma-induced photolysis of water suggests implications beyond studies of DNA and opens new vistas for using simple nanosecond lasers to probe how ultralow energy radiation may affect living matter under physiological conditions.

Comparison of double intravenous vasopressor automated system using nexfin versus manual vasopressor bolus administration for maintenance of haemodynamic stability during spinal anaesthesia for caesarean delivery: A randomised double-blind controlled trial.

BACKGROUND: Hypotension is a common side effect of spinal anaesthesia during caesarean delivery and is associated with maternal and foetal adverse effects. We developed an updated double intravenous vasopressor automated (DIVA) system that administers phenylephrine or ephedrine based on continuous noninvasive haemodynamic monitoring using the Nexfin device. OBJECTIVE: The aim of our present study is to compare the performance and reliability of the DIVA system against Manual Vasopressor Bolus administration. DESIGN: A randomised, double-blind controlled trial. SETTING: Single-centre, KK Women's and Children's Hospital, Singapore. PATIENTS: Two hundred and thirty-six healthy women undergoing elective caesarean delivery under spinal anaesthesia. MAIN OUTCOME MEASURES: The primary outcome was the incidence of maternal hypotension. The secondary outcome measures were reactive hypertension, total vasopressor requirement and maternal and neonatal outcomes. RESULTS: The DIVA group had a significantly lower incidence of maternal hypotension, with 39.3% (46 of 117) patients having any SBP reading less than 80% of baseline compared with 57.5% (65 of 113) in the manual vasopressor bolus group (P = 0.008). The DIVA group also had fewer hypotensive episodes than the manual vasopressor bolus group (4.67 versus 7.77%; P < 0.0001). There was no difference in the incidence of reactive hypertension or the total vasopressor requirement. The DIVA group had less wobble in system performance. Maternal and neonatal outcomes were similar. CONCLUSION: The DIVA system achieved better control of maternal blood pressure after spinal anaesthesia than manual vasopressor bolus administration. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02277730.

Effect of nucleants in photothermally assisted crystallization.

Laser-induced crystallization is emerging as a promising technique to crystallize biomolecules like amino acids and proteins. The use of external materials as nucleants and novel seeding methods open new paths for protein crystallization. We report here the results of experiments that explore the effect of nucleants on laser-based crystallization of microlitre droplets of small molecules, amino acids, and proteins. The role of parameters like solute concentration, droplet volume, type and size of the nucleant, and laser power, are systematically investigated. In addition to crystallization of standard molecules like NaCl, KCl, and glycine, we demonstrate the crystallization of negatively (l-histidine), and positively (l-aspartic acid) charged amino acids and lysozyme protein. Single crystal X-ray diffraction and Raman spectroscopy studies unequivocally indicate that the nucleants do not alter the molecular structure of glycine, hydrogen bonding patterns, and packing. Localized vaporization of the solvent near the nucleant due to photothermal heating has enabled us to achieve rapid crystallization - within 3 s - at laser intensities of 0.1 MW cm-2, significantly lower than those reported earlier, with both saturated and unsaturated solutions. The outcome of the current experiments may be of utility in tackling various crystallization problems during the formation of crystals large enough to perform X-ray crystallography.

A preliminary assessment of the LMA protector™ in non-paralysed patients.

BACKGROUND: The LMA Protector™ is the latest CE marked single use supraglottic airway device. This airway device provides access and functional separation of the respiratory and digestive tracts. There are two ports (male, female ports) to provide suction in the laryngeal region and insertion of the gastric tube. The aim of our study is to assess the ease of use, airway quality, device positioning, airway leak and complications associated with initial clinical experience in LMA Protector™ usage. METHODS: This is an initial investigation of LMA Protector™ airway device. We conducted a preliminary assessment in the anaesthetised women who underwent minor gynaecological procedures with spontaneous ventilation in order to evaluate the performance of the airway device. RESULTS: Insertion was successful on first and second attempts in 23 (88.5%) and 3 (11.5%) respectively. Median [IQR (range)] insertion time was 19 [17-21(14-58)] seconds. Airway leak pressure was 25.5 [23-29(21-30] cmH2O. On fibreoptic examination via the device, vocal cords were visible in all 26 patients. There were no alternative airway use or airway manipulations required during maintenance of anaesthesia. Six patients had sore throat 24 h after procedures and there was no dysphagia or hoarseness. CONCLUSION: This pilot study of the LMA protector shows that the device is easily inserted with fast insertion time, providing a reliable and adequate airway seal. TRIAL REGISTRATION: Clinicaltrials.gov Registration NCT02531256 . Retrospectively registered on August 21, 2015.

Idiopathic Calcinosis Cutis Universalis Treated Successfully with Oral Diltiazem-A Case Report.

Idiopathic calcinosis cutis is very rare and difficult to treat. Various medical modalities of treatment described with inconsistent results include chelating agents, colchicine, and probenecid. Calcium channel blockers are known to work by inhibiting intracellular entry of calcium. We successfully treated a case of idiopathic calcinosis cutis using oral diltiazem.

Impact of 'fire drill' training and dedicated obstetric resuscitation code in improving fetomaternal outcome following cardiac arrest in a tertiary referral hospital setting in Singapore.

Cardiac arrest in pregnancy is a rare but catastrophic obstetric emergency, with a quoted incidence of 1:20,000 pregnancies. Speedy multidisciplinary interventions are crucial for good maternal and foetal outcomes. A perimortem caesarean section (PMCS) initiated within 4 min of onset of cardiac arrest to minimise the effect of aortocaval compression on cardiopulmonary resuscitation (CPR) has been recommended as a key intervention, which is likely to improve survival of both mother and foetus. Sudden collapse is uncommon in pregnant women and their management is more challenging than in a non-pregnant patient. This article aims to emphasise the significance of early identification and management of impending or established maternal cardiac arrest. We propose that a focus on effective and good-quality CPR, utilising key interventions such as early airway control, left uterine displacement and a timely decision for a PMCS with multidisciplinary input is more likely to result in good maternal and foetal survival and neurological outcomes. We also discuss the role of 'fire drill' obstetric training for key staff and the use of a dedicated hospital-wide resuscitation code for managing collapse in obstetric patients in improving survival and outcomes. We present four cases of maternal cardiac arrest managed with PMCS in our hospital, highlighting the evolution in management and with improved outcomes following changes to our resuscitation guidelines, training and workflows.

Rotational dynamics of optically trapped human spermatozoa.

INTRODUCTION: Optical trapping is a laser-based method for probing the physiological and mechanical properties of cells in a noninvasive manner. As sperm motility is an important criterion for assessing the male fertility potential, this technique is used to study sperm cell motility behavior and rotational dynamics. METHODS AND PATIENTS: An integrated optical system with near-infrared laser beam has been used to analyze rotational dynamics of live sperm cells from oligozoospermic and asthenozoospermic cases and compared with controls. RESULTS: The linear, translational motion of the sperm is converted into rotational motion on being optically trapped, without causing any adverse effect on spermatozoa. The rotational speed of sperm cells from infertile men is observed to be significantly less as compared to controls. CONCLUSIONS: Distinguishing normal and abnormal sperm cells on the basis of beat frequency above 5.6 Hz may be an important step in modern reproductive biology to sort and select good quality spermatozoa. The application of laser-assisted technique in biology has the potential to be a valuable tool for assessment of sperm fertilization capacity for improving assisted reproductive technology.

Seventh-harmonic generation from tightly focused 2 µm ultrashort pulses in air.

We report generation of third, fifth and seventh harmonics from air by using tightly focused, ultrashort pulses of short-wave infrared (2 µm) radiation. We have measured the third- and fifth-harmonic efficiencies to be 5×10(-5) and ~1.4×10(-5), respectively, with the ratio of fifth-to-third-harmonic efficiency being close to 0.28. Our experimental results provide confirmation of expectations of the higher-order Kerr effect model.

Axicon-based writing of waveguides in BK7 glass.

We report on the direct writing of waveguide structures using an axicon lens to focus a 40 fs laser pulse within BK7 glass. The written structures are characterized for waveguiding action: waveguiding action for 635 and 1550 nm light and propagation loss as low as 0.19 dB/cm is measured. Loss values decrease with laser exposure time for incident energy of 300 µJ, indicating enhancement of index contrast. At higher energies, a reverse trend is obtained: higher loss values are obtained as index contrast degrades with an increase in exposure time.

A search for the sulphur hexafluoride cation with intense, few cycle laser pulses.

It is well established that upon ionization of sulphur hexafluoride, the SF6(+) ion is never observed in mass spectra. Recent work with ultrashort intense laser pulses has offered indications that when strong optical field are used, the resulting "bond hardening" can induce changes in the potential energy surfaces of molecular cations such that molecular ions that are normally unstable may, indeed, become metastable enough to enable their detection by mass spectrometry. Do intense, ultrashort laser pulses permit formation of SF6(+)? We have utilized intense pulses of 5 fs, 11 fs, and 22 fs to explore this possibility. Our results are negative: no evidence is discovered for SF6(+). However, multiply charged sulphur and fluorine ions from highly charged SF6(q+) ions are observed that enable us to resolve the controversy regarding the kinetic energy release accompanying formation of F(+) fragment ions. Quantum chemical computations of field-distorted potential energy curves of SF6 and its molecular ion enable us to rationalize our non-observation of SF6(+). Our findings have implications for high harmonic generation from SF6 in the few-cycle regime.

A Study of Correlation of Alopecia Areata and Metabolic Syndrome in Northwest Indian Population: A Case-Control Study.

Context: Alopecia areata (AA) is the most common cause of inflammatory, nonscarring hair loss, involving hair-bearing areas of the body. The etiology of AA still remains uncertain; however, genetic, environmental, and autoimmunity play a role. Newer theories such as oxidative theory, HPA axis activation, and finally, the role of increased inflammatory cytokines such as interleukin 1 (IL1), tumor necrosis factor-alpha, interferon-gamma, IL-2 IL-4, and MIF are suggested to contribute to both AA and metabolic syndrome (MS). Aims: Assessment of the degree of association of MS (NCEP ATP III criteria) in clinically diagnosed cases of AA and compare to that of controls. Materials and Methods: Similar age/sex-matched AA patients and controls (106 in each group) were taken. Anthropometric measurements, blood-sugar estimation, lipid-profile estimation in venous blood sample, and blood-pressure measurement were done. Results: Prevalence of MS was almost similar among cases of AA 9/106 (8.47%) as well as healthy controls 8/106 (7.54%), and the difference was not statistically significant (P = 1). Among all components of MS, waist circumference (WC) (central obesity) was the most common parameter (100% cases). In controls, high systolic blood pressure (SBP) was the most common parameter (77.78% controls). AA is associated with a higher level of SBP, diastolic blood pressure (DBP), WC although nonsignificant, and low level of high-density lipoprotein cholesterol which was the only significant association. Conclusion: Insignificant correlation between occurrence of MS and evidence of insulin resistance (IR) in AA was observed in this study population. However, some of the observations in the present study may raise awareness in susceptible individuals that lifestyle changes and regular screening in AA can reduce the risk of cardiovascular diseases and other co-existing autoimmune inflammatory condition-IR, dyslipidemia, and hypertension.

Quantum dynamics of H2+ in intense laser fields on time-dependent potential energy surfaces.

We have exploited the fully time-dependent Born-Oppenheimer approximation to develop time-dependent potential energy surfaces for the lowest two states of H(2)(+) in the presence of intense, time-varying, few-cycle laser fields of 2-8 fs duration. Quantum dynamics are explored on these field-dressed, time-dependent potentials. Our results show that the potential well in the lowest-energy state of H(2)(+) (i) collapses as the laser pulse reaches its peak amplitude and (ii) regains its form on the trailing edge of the pulse, and (iii) the trapped nuclear wavepacket has a higher probability of leaking out from the well in the case of longer laser pulses. The carrier envelope phase is found to have negligible effect on the nuclear dynamics.

Quantum dynamics of proton migration in H2O dications: H2+ formation on ultrafast timescales.

Irradiation of isolated water molecules by few-cycle pulses of intense infrared laser light can give rise to ultrafast rearrangement resulting in formation of the H(2) (+) ion. Such unimolecular reactions occur on the potential energy surface of the H(2)O(2+) dication that is accessed when peak laser intensities in the 10(15) W cm(-2) range and pulse durations as short as 9-10 fs are used; ion yields of ~1.5% relative to the H(2)O(+) ion are measured. We also study such reactions by means of time-dependent wavepacket dynamics on an ab initio potential energy surface of the dication and show that a proton, generated from O-H bond rupture, migrates towards the H-atom, and forms vibrationally excited H(2)(+) in a well-defined spatial zone.

Tank treading of optically trapped red blood cells in shear flow.

Tank-treading (TT) motion is established in optically trapped, live red blood cells (RBCs) held in shear flow and is systematically investigated under varying shear rates, temperature (affecting membrane viscosity), osmolarity (resulting in changes in RBC shape and cytoplasmic viscosity), and viscosity of the suspending medium. TT frequency is measured as a function of membrane and cytoplasmic viscosity, the former being four times more effective in altering TT frequency. TT frequency increases as membrane viscosity decreases, by as much as 10% over temperature changes of only 4°C at a shear rate of ∼43 s(-1). A threshold shear rate (1.5 ± 0.3 s(-1)) is observed below which the TT frequency drops to zero. TT motion is also observed in shape-engineered (spherical) RBCs and those with cholesterol-depleted membranes. The TT threshold is less evident in both cases but the TT frequency increases in the latter cells. Our findings indicate that TT motion is pervasive even in folded and deformed erythrocytes, conditions that occur when such erythrocytes flow through narrow capillaries.

A study of biophysical profile of inguinal skin: An implication for health and disease.

CONTEXT: Inguinal skin is prone to various infectious dermatological conditions such as erythrasma, intertrigo, hidradenitis suppurativa, folliculitis, dermatophytic infection, and various sexually transmitted diseases, as compared to the skin elsewhere. AIM: Our study attempts to compare the biophysical profile parameters (BPPs) of the genital skin with that of the rest of the body, while taking skin of the upper back as control. It also attempts to find out if there is a difference in BPPs of the two sites and that how the change in the BPPs, bring about change in microbiome and make inguinal skin more prone to infections. MATERIALS AND METHODS: This was a hospital-based comparative study conducted over 976 patients (600 males and 376 females) of age group 18-60 years, where BPP parameters such as hydration, skin pH, transepidermal water loss (TEWL), and sebum content were measured over the skin of the upper back and right inguinal region, and the results were summarized and presented as proportions (%). Chi-square test was used to compare abnormal findings. P ≤ 0.05 was taken as statistically significant. MedCalc 16.4 version software was used for all statistical calculations. RESULTS: Significant difference was noted in skin pH and TEWL, where P value came out to be <0.05, which was statistically significant, whereas there was minimal difference in sebum content and skin hydration in both the areas, in males and females. CONCLUSION: Raised skin pH disturbs organization of lipid bilayers (disturbed barrier), decreases lipid processing (impaired SC cohesion), and increases serine protease activity (reduced AMP). Increased TEWL (defect in physical barrier) and decreased hydration predispose the genital skin to infections. Use of pH buffered solutions (3-4), barrier repair creams containing ceramides, and barrier protective creams with dimethicone can help prevent these inguinal dermatoses.