ANTI-THYROID ANTIBODIES AND THE GONADOTROPHINS PROFILE (LH/FSH) IN EUTHYROID POLYCYSTIC OVARIAN SYNDROME WOMEN.

Context: The current study aimed to determine association of anti-TPO with LH/FSH in PCOS women. Design: Current case control study included 33 diagnosed PCOS women and 32 age matched healthy women and were analysed for body mass index (BMI) and waist to hip ratio (WHR), fasting blood glucose (FBG), free T3 (FT3), free T4 (FT4), Thyroid stimulating hormone (TSH), dehydroepiandrostenedione (DHEA-S), total testosterone, follicular stimulating hormone (FSH), luteinizing hormone (LH) and anti thyroperoxidase antibodies (anti-TPO). Data was statistically analysed by Student's t - test and Pearson's correlation analysis. Results: Of the total PCOS women, 45% were obese and 34.37% had raised anti-TPO. The biochemical profile of obese PCOS women showed significantly raised FBG (p<0.0001), LH (p<0.0001), Testosterone (p<0.0001) and DHEA-S (p=0.0021) as compared to non-obese PCOS women. The LH/FSH ratio was significantly raised in PCOS women as compared to control (p<0.0001). Pearson's correlation analysis showed a significant association of anti-TPO with FBS, testosterone, LH and LH/FSH in obese PCOS and with Testosterone and LH in non-obese PCOS women using SPSS 21. Conclusion: The current study shows a high prevalence of AITD in euthyroid PCOS women and suggests a strong link of euthyroid obese PCOS women to autoimmunity due to the hyper-anderogenism and a higher LH/FSH ratio.

Size-dependent synergetic seeding effects in the inspection of airborne dry nanoaerosols by LIBS.

In the present paper, confined dry Cu nanoaerosols of controlled particle size are inspected under a time-resolved LIBS scheme to explore the effect of laser-particulate matter interaction upon the detection capability of airborne nanoparticulate material. Optically catapulted streams probed showed linear intensity vs mass correlation and similar signal stability which is linked to the seeding effect caused by smaller particles yielding hotter, albeit shorter plasmas. Seeding effect is demonstrated by hyperspectral time-resolved aerosol inspection, which exposes both, the interaction between multiple plasma nuclei and the discrete nature of the laser-particle interaction. Observed population/exhaustion cycles at the focal volume of the inspection laser explained the uncertainty values characteristic of LIBS inspection of aerosols. A thorough inspection of the emission in time evidenced a significantly different evolution of the intensity profile for commonly monitored Cu lines owed not only to the nature of the monitored transit and pulse energy, but also to particle size. These results suggest that the experimental settings for quantitative ultrafine aerosol inspection need to be tuned according to the target particle size and the particle density of the aerosol as seeding effects facilitates signal saturation, therefore this effect simultaneously contributes to and detracts from the analytical performance of LIBS on nanometric aerosols.

CRISPR/Cas-New Molecular Scissors in Diagnostics and Therapeutics of COVID-19.

The current pandemic of COVID-19, with its climbing number of cases and deaths, has us searching for tools for rapid, reliable, and affordable methods of detection on one hand, and novel, improved therapeutic strategies on the other. The currently employed RT-PCR method, despite its all-encompassing utility, has its shortcomings. Newer diagnostic tools, based on the Clustered Regularly Interspaced Short Palindromic Repeats/Cas(CRISPR-Cas) system, with its better diagnostic accuracy measures, have come up to fill that void. These assay platforms are expected to slowly take up the place of COVID-19 diagnostics. Further, the current therapeutic options focus mainly on counteracting the viral proteins and components and their entry into host cells. The CRISPR-based system, especially through the RNA-guided Cas13 approach, can identify the genomic characteristics of SARS-CoV-2 and provide a novel inhibition strategy for coronaviruses. In this mini-review, we have discussed the available and upcoming CRISPR-based diagnostic assays and the potential of the CRISPR/Cas system as a therapeutic or prevention strategy in COVID-19. CRISPR-Cas system shows promise in both diagnostics as well as therapeutics and may as well change the face of molecular diagnosis and precision medicine.

Effect of karwanda (Carissa congesta Wight) and sugar addition on physicochemical characteristics of ash gourd (Benincasa hispida) and bottle gourd (Langenaria siceraria) based beverages.

There is a clear trend towards increasing consumption of juices as they can reduce imbalance of redox potential and provide necessary health benefits to consumers. Levels of karwanda (Carissa congesta Wight) and vegetable juices were varied to prepare nine different formulations of ash gourd-karwanda (AgK) and bottle gourd-karwanda blends (BgK) of higher nutritive, sensory qualities and storability. Total polyphenols (TP), antioxidant activity (AOA), total soluble solids and acidity were increased significantly (p ≤ 0.05) with addition of karwanda. AgK blend (35:35) and BgK blend (35:30) were selected based on their higher overall acceptability, TP and AOA. AgK blends had higher α-amylase (31%) while BgK blends had higher α-glucosidase (43%) inhibitory activities. Concentration of TP and anthocyanins decreased significantly (p < 0.05), AOA remained unchanged and anti-inflammatory activities decreased (33-38%) in AgK and BgK blends during accelerated storage at 50 °C for 12 days. Addition of sugar in BgK blend decreased stability of TP (11%), flavonoids (31%) and anthocyanins (8%). During in vitro gastrointestinal digestion, TP, flavonoids and anthocyanins reduction rate was significantly higher for BgK blend with sugar.

Hypocalcemia in an 11 Year Old Child: A Difficult Case to Treat.

Hypocalcemia is a laboratory and clinical abnormality that is observed especially in neonates and paediatric patients. Laboratory hypocalcaemia is often asymptomatic but it can manifest as central nervous system irritability, paraesthesia, tetany (i.e. contraction of hands, arms, feet, larynx, bronchioles), seizures, and even psychiatric changes in children. Cardiac function may also be impaired because of poor muscle contractility. We report a unique case of an eleven year old male child who presented with chronic kidney disease associated with severe hypocalcemia, tonic-clonic seizures, hypovitaminosis D but normal electroencephalogram and electrocardiography. The child required prolonged intravenous calcium gluconate therapy to correct his ionised calcium levels.

EFhd2/Swiprosin-1 is a common genetic determinator for sensation-seeking/low anxiety and alcohol addiction.

In many societies, the majority of adults regularly consume alcohol. However, only a small proportion develops alcohol addiction. Individuals at risk often show a high sensation-seeking/low-anxiety behavioural phenotype. Here we asked which role EF hand domain containing 2 (EFhd2; Swiprosin-1) plays in the control of alcohol addiction-associated behaviours. EFhd2 knockout (KO) mice drink more alcohol than controls and spontaneously escalate their consumption. This coincided with a sensation-seeking and low-anxiety phenotype. A reversal of the behavioural phenotype with ß-carboline, an anxiogenic inverse benzodiazepine receptor agonist, normalized alcohol preference in EFhd2 KO mice, demonstrating an EFhd2-driven relationship between personality traits and alcohol preference. These findings were confirmed in a human sample where we observed a positive association of the EFhd2 single-nucleotide polymorphism rs112146896 with lifetime drinking and a negative association with anxiety in healthy adolescents. The lack of EFhd2 reduced extracellular dopamine levels in the brain, but enhanced responses to alcohol. In confirmation, gene expression analysis revealed reduced tyrosine hydroxylase expression and the regulation of genes involved in cortex development, Eomes and Pax6, in EFhd2 KO cortices. These findings were corroborated in Xenopus tadpoles by EFhd2 knockdown. Magnetic resonance imaging (MRI) in mice showed that a lack of EFhd2 reduces cortical volume in adults. Moreover, human MRI confirmed the negative association between lifetime alcohol drinking and superior frontal gyrus volume. We propose that EFhd2 is a conserved resilience factor against alcohol consumption and its escalation, working through Pax6/Eomes. Reduced EFhd2 function induces high-risk personality traits of sensation-seeking/low anxiety associated with enhanced alcohol consumption, which may be related to cortex function.

Fibroids and Infertility.

The precise impact of fibroids, which are the most common benign gynaecological tumours in women, on reproductive function and infertility is unknown. The need to treat submucosal fibroids is widely accepted, but fibroids in other locations and sizes continue to present a clinical conundrum. This article examines the mechanisms by which fibroids affect implantation and fertility, and stratifies their impact on basis of size, location and nature. It also explores the evidence base of the available treatment modalities in specific relation to improving fertility outcomes. Traditionally, a myomectomy has been advocated to treat fibroids for the reproductive population; however, as well as evaluating the benefits of surgery including endoscopic, this article explores alternative therapies including medical and radiological interventions.

Molecular mechanisms of the effect of ultrasound on the fibrinolysis of clots.

BACKGROUND: Ultrasound accelerates tissue-type plasminogen activator (t-PA)-induced fibrinolysis of clots in vitro and in vivo. OBJECTIVE: To identify mechanisms for the enhancement of t-PA-induced fibrinolysis of clots. METHODS: Turbidity is an accurate and convenient method, not previously used, to follow the effects of ultrasound. Deconvolution microscopy was used to determine changes in structure, while fluorescence recovery after photobleaching was used to characterize the kinetics of binding/unbinding and transport. RESULTS: The ultrasound pulse repetition frequency affected clot lysis times, but there were no thermal effects. Ultrasound in the absence of t-PA produced a slight but consistent decrease in turbidity, suggesting a decrease in fibrin diameter due solely to the action of the ultrasound, likely caused by an increase in protofibril tension because of vibration from ultrasound. Changes in fibrin network structure during lysis with ultrasound were visualized in real time by deconvolution microscopy, revealing that the network becomes unstable when 30-40% of the protein in the network was digested, whereas without ultrasound, the fibrin network was digested gradually and retained structural integrity. Fluorescence recovery after photobleaching during lysis revealed that the off-rate of oligomers from digesting fibers was little affected, but the number of binding/unbinding sites was increased. CONCLUSIONS: Ultrasound causes a decrease in the diameter of the fibers due to tension as a result of vibration, leading to increased binding sites for plasmin(ogen)/t-PA. The positive feedback of this structural change together with increased mixing/transport of t-PA/plasmin(ogen) is likely to account for the observed enhancement of fibrinolysis by ultrasound.

Time-resolved x-ray diffraction techniques for bulk polycrystalline materials under dynamic loading.

We have developed two techniques for time-resolved x-ray diffraction from bulk polycrystalline materials during dynamic loading. In the first technique, we synchronize a fast detector with loading of samples at strain rates of ~10(3)-10(4) s(-1) in a compression Kolsky bar (split Hopkinson pressure bar) apparatus to obtain in situ diffraction patterns with exposures as short as 70 ns. This approach employs moderate x-ray energies (10-20 keV) and is well suited to weakly absorbing materials such as magnesium alloys. The second technique is useful for more strongly absorbing materials, and uses high-energy x-rays (86 keV) and a fast shutter synchronized with the Kolsky bar to produce short (~40 µs) pulses timed with the arrival of the strain pulse at the specimen, recording the diffraction pattern on a large-format amorphous silicon detector. For both techniques we present sample data demonstrating the ability of these techniques to characterize elastic strains and polycrystalline texture as a function of time during high-rate deformation.

Effect of mixed surfactants on stratum corneum: a drying stress and Raman spectroscopy study.

OBJECTIVE: Stratum corneum (SC) lipids are known to play an important role in barrier properties of skin by maintaining the optimal hydration levels. The disruption of SC lipids by cleanser surfactants is believed to lead to dry skin damage which can be a precursor to other skin disorders. The purpose of this study is to investigate the effects of commonly used anionic and zwitterionic surfactants sodium lauryl ether sulphate (SLES) and cocoamidopropyl betaine (CAPB) on the generation of drying stresses in SC and the role played by lipids. METHODS: Stratum corneum separated from pig skin was treated with various surfactants (SDS, SLES and CAPB) their mixtures and solvents. The tensile response to these treatments was measured by using a dynamic mechanical thermal analyzer. A Raman spectroscopy study of the treated samples was performed to investigate the effects of lipid modification (lipid chain conformational order and lipid removal) on stress generation in SC. RESULTS: The effects of commonly used anionic and zwitterionic surfactants on the generation of drying stresses in SC were studied. Although known to be milder in comparison with SDS, both SLES and CAPB generated high drying stresses individually. In mixtures, SLES-CAPB at 4 : 1 ratio leads to lower drying stress as compared to water alone. A Raman spectroscopic study of surfactant-treated SC shows changes in lipid chain conformational order as well as a decrease in lipid-protein ratio in SC. A chloroform-methanol 2 : 1 treatment leads to the highest drying stress as well delipidization of SC. CONCLUSION: The results show a correlation between generation of drying stress in SC and extent of lipid modification. We propose that the changes in lipid conformational order and removal of lipid components affect the stress relaxation properties of SC leading to high drying stresses.

Fetal hemoglobin and alpha thalassemia modulate the phenotypic expression of HbSD-Punjab.

INTRODUCTION: HbSD-Punjab (HbSD) is a less common form of sickle cell disease (SCD) and discrimination between HbSD and HbSS is not possible on alkaline electrophoresis because the two variants overlap in the compound heterozygous state. There are only a few publications consisting mostly of case reports. Thus, the phenotypic expression of HbSD and its modifiers has not been studied. METHODS: We studied the phenotypic expression of 42 cases of HbSD (the largest number of subjects ever included in this kind of study) and compared them with 84 HbSS cases matched for age, sex, and caste. Further, we evaluated the influence of HbF concentration and alpha thalassemia on the phenotypic expressions of HbSD, namely the frequency of VOC and degree of hemolysis. RESULTS: The frequencies of VOC were similar in both the groups. The markers of hemolysis such as total bilirubin, unconjugated bilirubin, and LDH were higher where as HbF concentration was significantly low in HbSD. There was a negative correlation between HbF concentration and risk of VOC in the HbSD. The total hemoglobin level and hematocrit were significantly high, and the MCV and MCH were significantly low in HbSD with alpha thalassemia. Alpha thalassemia had no influence on the frequency of VOC and severity of hemolysis in HbSD. CONCLUSION: HbF reduced the frequency of VOC but had no influence on the hemolytic markers in HbSD. HbSD with alpha thalassemia was associated with hypohromic and microcytic features of red blood cells.

Clinical and molecular characterization of Hb Hofu in eastern India.

INTRODUCTION: Hb Hofu (HBB:c. 380T>A) is a rare inherited hemoglobin abnormality with few case reports in the world literature. METHODS: Screening for the sickle cell gene mutation and other hemoglobinopathies was carried out using the sickle slide test, Hb electrophoresis, and HPLC under an ongoing central government project. RESULTS: We detected twelve Hb Hofu heterozygotes and three sickle Hb Hofu compound heterozygotes. The heterozygotes were asymptomatic except for one individual who had chronic kidney disease and moderate anemia. Only one HbS-Hofu case was symptomatic and presented with intermittent attacks of painful crisis. In the carrier state, the Hb Hofu eluted as a hump at the beginning of the HbA(0) window. But in HbS-Hofu cases, Hb Hofu eluted as a single peak in the HbA(0) window, with the HbA(2) levels being >4% consistently. CONCLUSION: HbS-Hofu has a variable clinical presentation. The retention time of Hb Hofu on HPLC is very close to that of HbA(0) and often elutes in the A0 window. Thus, there is every possibility of the HbS-Hofu chromatogram to be misinterpreted as that of a sickle cell trait/transfused sickle cell-beta-thalassemia case. This is the first time where Hb Hofu has been detected by HPLC, which is the widely accepted screening technique for hemoglobinopathies around the world.

Polymer/surfactant interactions and nanostructures: current development for cleansing, release, and deposition of actives.

Nature exhibits a variety of remarkable phenomena that are useful but difficult to be imitated in real life. Examples are a "touch me not" plant folding up upon being attacked or microbes depositing on ocean vessels even under hostile conditions. Understanding of mechanisms governing these phenomena can prove powerful for developing new classes of cosmetic products. Systems based on polymer/surfactant colloid chemistry are being developed for achieving transport and release of cosmetic and pharmaceutical molecules at desired rates and desired sites. Modifications of the surfactants and polymers provide cleansing properties such as scavenging of odor and sebaceous body excretions and controlled delivery and deposition of sensory/hygienic attributes. New surfactants (sugar based and bio surfactants), hybrid polymers (silicone based and hydrophobically modified) and nanogels have been recently synthesized which may have applications in fields of cosmetics/fragrances/drugs etc. Due to the associative nature of the hydrophobic groups, hybrid polymers can form intramolecular nanodomains at all concentrations of the polymer and inter-molecular aggregates at high concentrations. New hybrid polymers and nano-gel particles can be developed with ability to extract and deliver actives by varying such properties as swelling/shrinking capacity and sensitivity to temperature, shear and dilution. Control of such properties as size, shape and cross linking of nanohybrid particles offer maximum opportunity for producing families of nanovehicles in personal and homecare industry. This review article provides an insight into current developments in field of nano-surfactant science, comprising discussions on nanogel particles, hybrid polymer and liposomes.

The role of the amino acid residue at alpha1:189 in the binding of neuromuscular blocking agents to mouse and human muscle nicotinic acetylcholine receptors.

BACKGROUND AND PURPOSE: Nicotinic acetylcholine receptors (AChRs) are valuable therapeutic targets. To exploit them fully requires rapid assays for the evaluation of potentially therapeutic ligands and improved understanding of the interaction of such ligands with their receptor binding sites. EXPERIMENTAL APPROACH: A variety of neuromuscular blocking agents (NMBAs) were tested for their ability to inhibit the binding of [(125)I]alpha-bungarotoxin to TE671 cells expressing human muscle AChRs. Association and dissociation rate constants for vecuronium inhibition of functional agonist responses were then estimated by electrophysiological studies on mouse muscle AChRs expressed in Xenopus oocytes containing either wild type or mutant alpha1 subunits. KEY RESULTS: The TE671 inhibition binding assay allowed for the rapid detection of competitive nicotinic AChR ligands and the relative IC(50) results obtained for NMBAs agreed well with clinical data. Electrophysiological studies revealed that acetylcholine EC(50) values of muscle AChRs were not substantially altered by non-conservative mutagenesis of phenylalanine at alpha1:189 and proline at alpha1:194 to serine. However the alpha1:Phe189Ser mutation did result in a 3-4 fold increase in the rate of dissociation of vecuronium from mouse muscle AChRs. CONCLUSIONS AND IMPLICATIONS: The TE671 binding assay is a useful tool for the evaluation of potential therapeutic agents. The alpha1:Phe189Ser substitution, but not alpha1:Pro194Ser, significantly increases the rate of dissociation of vecuronium from mouse muscle AChRs. In contrast, these non-conservative mutations had little effect on EC(50) values. This suggests that the AChR agonist binding site has a robust functional architecture, possibly as a result of evolutionary 'reinforcement'.

Study of properties of modified silicones at solid-liquid interface: fabric-silicone interactions.

Silicones are special reagents that impart desired surface properties such as softness, bounciness and antiwrinkle properties to fabrics and related materials. Although these finishing processes have been practiced routinely, very little is known about the mechanisms involved in modification so that they could be improved. The current study was undertaken to develop basic understanding of the mechanisms responsible for surface modification of fibers using silicones. PDMS based amino silicone emulsions, quaternized to various degrees using dimethyl sulphate, were used in the present study. The electrokinetic properties of the modified silicones were studied as a function of pH. It was expected that the silicone emulsions would show a steady positive zeta potential throughout the pH range due to the quaternization by dimethyl sulphate. Surprisingly, a sudden drop in the zeta potential was observed around pH 8 with the samples turning hazy in the pH range of 8-10. Turbidimetric studies also showed a sudden increase in the turbidity in the pH range 8-10 where commercial processes also encounter problems. It was concluded that the emulsions were destabilized at pH 8-10 thus rendering them ineffective for surface treatment. In order to identify reason for the improvement in fabric properties, fiber structure was monitored using atomic force microscopy. It was observed that the treated fibers were far smoother, relaxed and uniform as compared to the untreated fibers. Thus the morphology of the fabric is modified in a specific way by treatment with specialty silicones.

Effect of supercoiling on formation of protein-mediated DNA loops.

DNA loop formation is one of several mechanisms used by organisms to regulate genes. The free energy of forming a loop is an important factor in determining whether the associated gene is switched on or off. In this paper we use an elastic rod model of DNA to determine the free energy of forming short (50-100 basepair), protein mediated DNA loops. Superhelical stress in the DNA of living cells is a critical factor determining the energetics of loop formation, and we explicitly account for it in our calculations. The repressor protein itself is regarded as a rigid coupler; its geometry enters the problem through the boundary conditions it applies on the DNA. We show that a theory with these ingredients is sufficient to explain certain features observed in modulation of in vivo gene activity as a function of the distance between operator sites for the lac repressor. We also use our theory to make quantitative predictions for the dependence of looping on superhelical stress, which may be testable both in vivo and in single-molecule experiments such as the tethered particle assay and the magnetic bead assay.

Pulmonary infection with Serratia marcescens.

A case of pulmonary infection, presenting with fever and productive cough (pseudohaemoptysis) was diagnosed as having infection with Serratia marcescens on performing culture and sensitivity tests. The organism was confirmed upto species level using the standard biochemical tests.

Sequence-specific interaction between HIV-1 matrix protein and viral genomic RNA revealed by in vitro genetic selection.

The human immunodeficiency virus type-1 matrix protein (HIV-1 MA) is a multifunctional structural protein synthesized as part of the Pr55 gag polyprotein. We have used in vitro genetic selection to identify an RNA consensus sequence that specifically interacts with MA (Kd = 5 x 10(-7) M). This 13-nt MA binding consensus sequence bears a high degree of homology (77%) to a region (nt 1433-1446) within the POL open reading frame of the HIV-1 genome (consensus sequence from 38 HIV-1 strains). Chemical interference experiments identified the nucleotides within the MA binding consensus sequence involved in direct contact with MA. We further demonstrate that this RNA-protein interaction is mediated through a stretch of basic amino acids within MA. Mutations that disrupt the interaction between MA and its RNA binding site within the HIV-1 genome resulted in a measurable decrease in viral replication.

Comparison of the effects of intravenous pamidronate and oral clodronate on symptoms and bone resorption in patients with metastatic bone disease.

BACKGROUND: There is considerable debate as to the optimum schedule of bisphosphonate treatment in advanced malignancy. Short term studies using symptomatic response and biochemical markers of bone resorption may provide useful insight into differences between agents. PATIENTS AND METHODS: Fifty-one patients with metastatic bone disease were randomly allocated to either oral clodronate 1,600 mg daily (group 1), intravenous clodronate followed by the same schedule of oral clodronate (group 2). or intravenous pamidronate 90 mg monthly (group 3). No radiotherapy was delivered or other systemic anticancer treatments were allowed except for long term endocrine therapy. Bone resorption was assessed by measurement of urinary collagen crosslinks. At each visit a pain score was recorded. RESULTS: Symptomatic response was more frequent in the pamidronate group than in patients receiving clodronate. Nine of sixteen patients experienced a sustained improvement in pain score in the pamidronate-treated group, in contrast to only 4 of 16 and 2 of 11 patients in groups 1 and 2, respectively. There was a significant improvement in pain scores in the pamidronate arm compared with the clodronate treated patients after both three months of treatment (P <0.01) and at the last measurement (P <0.05). Biochemical changes correlated with changes in the pain score (P = 0.01). CONCLUSION: Intravenous pamidronate appears to be more effective than oral clodronate in both controlling symptoms and suppressing bone resorption.

Atomization mechanism and determination of Ag, Be, Cd, Li, Na, Sn and Zn in uranium-plutonium matrices by ETA-AAS.

The atomization processes involved in the Electrothermal Atomization-Atomic Absorption Spectrometric (ETA-AAS) determination of Ag, Be, Cd, Li, Na, Sn and Zn in the presence of an uranium-plutonium matrix containing 25% Pu have been investigated. The significant fall in the absorbance signal for Ag, Cd, Na and Zn in an uranium matrix and its restoration in the presence of plutonium is probably correlated with the change in the partial pressure of oxygen released from the matrix at/below the signal appearance temperature (T(app)). In case of Li and Sn, the signal remains unaffected irrespective of the U-Pu matrix which might be due to a high T(app) for these analytes. Regarding Be, the steep suppression of the signal in the presence of the plutonium matrix compared to an uranium matrix can be ascribed to the formation of stable Pu-Be compounds (PuBe(13)). Based on these studies, analytical procedures have been developed for the direct determination of nanogram amounts of these analytes in an U-Pu matrix with an average precision of 9% RSD.