Blood within the bone: orbital intraosseous venous malformation.

PURPOSE: Description of clinical features, radiological characteristics, and management strategies in primary orbital intraosseous venous malformation (OIVM) with pertinent literature review. METHODS: A retrospective analysis including clinical, radiologic, operative, and histopathological data of six cases of histopathologically proven OIVM was done. A comprehensive literature review was conducted using online databases and augmented with manual search to identify reported cases of OIVM. RESULTS: Study data showed five females and one male in young to middle-age group, with an average age of 30 years (range: 20-48 years). Proptosis was noted in five cases (83.33%), and the duration of symptoms ranged from 6 months to 10 years. Frontal and zygomatic bones were most frequently affected and expansile bony lesion was the most common CT scan finding. Three patients underwent pre-operative embolization of feeders followed by en bloc excision of mass and surgical reconstruction (50%); one patient was managed with partial excision (16.66%) while two were regularly followed-up after incision biopsy (33.33%). Histopathology revealed vascular spaces with endothelial lining, separated by bony trabeculae in all patients. Follow-up periods ranged from 6 to 48 months and no recurrence or progression were noted. CONCLUSIONS: OIVM is an exceptionally rare disorder with a gradually progressive benign course. Ophthalmologists need to be mindful of this entity during patient evaluation as it has propensity for large volume blood loss intra-operatively, owing to its vascular nature. Complete excision with reconstruction of resultant defect is the preferred treatment strategy and without known recurrence.

Rhodamine 6G-based efficient chemosensor for trivalent metal ions (Al3+, Cr3+ and Fe3+) upon single excitation with applications in combinational logic circuits and memory devices.

A new rhodamine 6G-based chemosensor (L3) was synthesized and characterized by 1H, 13C, IR and mass spectroscopy studies. It exhibited an excellent selective and sensitive CHEF-based recognition of trivalent metal ions M3+ (M = Fe, Al and Cr) over mono and di-valent and other trivalent metal ions with prominent enhancement in the absorption and fluorescence intensity for Fe3+ (669-fold), Al3+ (653-fold) and Cr3+ (667-fold) upon the addition of 2.6 equivalent of these metal ions in the probe in H2O/CH3CN (7 : 3, v/v, pH 7.2). The corresponding Kd values were evaluated to be 1.94 × 10-5 (Fe3+), 3.15 × 10-5 (Al3+) and 2.26 × 10-5 M (Cr3+). The quantum yields of L3, [L3-Fe3+], [L3-Al3+] and [L3-Cr3+] complexes in H2O/CH3CN (7 : 3, v/v, pH 7.2) were found to be 0.0005, 0.335, 0.327 and 0.333, respectively, using rhodamine-6G as the standard. The LODs for Fe3+, Al3+ and Cr3+ were determined by 3σ methods and found to be 2.57, 0.78 and 0.47 µM, respectively. The cyanide ion snatched Fe3+ from the [Fe3+-L3] complex and quenched its fluorescence via its ring-closed spirolactam form. Advanced level molecular logic devices using different inputs (2 and 4 input) and a memory device were constructed.

Dual Functionalized Injectable Hybrid Extracellular Matrix Hydrogel for Burn Wounds.

Low strength and rapid biodegradability of acellular dermal matrix (ADM) restrict its wider clinical application as a rapid cell delivery platform in situ for management of burn wounds. Herein, the extracted ADM was modified by a dual cross-linking approach with ionic crosslinking using chitosan and covalent cross-linking using an iodine-modified 2,5-dihydro-2,5-dimethoxy-furan cross-linker, termed as CsADM-Cl. In addition, inherent growth factors and cytokines were found to be preserved in CsADM-Cl, irrespective of ionic/covalent crosslinking. CsADM-Cl demonstrated improvement in post crosslinking stiffness with a decreased biodegradation rate. This hybrid crosslinked hydrogel supported adhesion, proliferation, and migration of human foreskin-derived fibroblasts and keratinocytes. Also, the angiogenic potential of CsADM-Cl was manifested by chick chorioallantoic membrane assay. CsADM-Cl showed excellent antibacterial activity against Escherichia coli and Staphylococcus aureus. Moreover, CsADM-Cl treated full thickness burn wounds and demonstrated rapid healing marked with superior angiogenesis, well-defined dermal-epidermal junctions, mature basket weave collagen deposition, and development of more pronounced secondary appendages. Altogether, the bioactive CsADM-Cl hydrogel established significant clinical potential to support wound healing as an apt injectable antibacterial matrix to encounter unmet challenges concerning critical burn wounds.

Effects of Molar Ratios of Two Immiscible Monomers toward Development of an Amphiphilic, Highly Stretchable, Bioadhesive, Self-Healing Copolymeric Hydrogel and its Mineral-Active Cellular Behavior.

Here, we report the striking properties such as high stretchability, self-healing, and adhesiveness of an amphiphilic copolymeric hydrogel (poly(acrylic acid)-poly(methyl methacrylate) (PAA-PMMA) gel) synthesized from two immiscible monomers-acrylic acid (AA) and methyl methacrylate (MMA)-through a simple free radical polymerization in an aqueous medium. The developed hydrogel, with a specific molar ratio of MMA and AA, is self-healable, which is attributed to the hydrophobic interaction arising from methyl groups of PMMA, as well as the breakdown and reformation of sacrificial noncovalent cross-linking through the weak hydrogen bonds between the carboxylic acid groups of PAA and methoxy groups of PMMA. The energy dissipation values in the hysteresis test signify the excellent self-recoverability of the hydrogel. The developed hydrogel showed adhesive behavior to the surfaces of polystyrene, glass, wood, metal, stone, ceramics, pork skin, and human skin. The physical and mechanical properties of the PAA-PMMA gel were fine-tuned through changes in the MMA/AA ratio and pH. Moreover, the PAA-PMMA hydrogel can serve as a template for calcium phosphate mineralization to yield a hydrogel composite, which improved MC3T3 cell adhesion and proliferation. Overall, we propose that depending on synthesis parameters and other scenarios, the synthesized PAA-PMMA hydrogel could potentially be employed in varying biomedical and industrial applications.

A differentially selective probe for trivalent chemosensor upon single excitation with cell imaging application: potential applications in combinatorial logic circuit and memory devices.

A new rhodamine 6G-benzylamine-based sensor (L1), having only hydrocarbon skeletons in the extended part, was synthesized and characterized by single-crystal X-ray crystallographic study. It exhibited excellent selective and sensitive recognition of trivalent metal ions M3+ (M = Fe, Al and Cr) over mono- and di-valent and other trivalent metal ions. A large enhancement of the fluorescence intensity for Fe3+ (41-fold), Al3+ (31-fold) and Cr3+ (26-fold) was observed upon the addition of 3.0 equivalent of these metal ions into the probe in H2O/CH3CN (4 : 1, v/v, pH 7.2) with naked eye detection. The corresponding Kf values were evaluated to be 9.4 × 103 M-1 (Fe3+), 1.34 × 104 M-1 (Al3+) and 8.7 × 103 M-1 (Cr3+). Quantum yields of the L1, [L1-Fe3+], [L1-Al3+] and [L1-Cr3+] complexes in H2O/CH3CN (4 : 1, v/v, pH 7.2) were found to be 0.012, 0.489, 0.376 and 0.310, respectively, using rhodamine-6G as standard. LODs for Fe3+, Al3+ and Cr3+ were determined by 3σ methods and found to be 1.28, 1.34 and 2.28 µM, respectively. Cyanide ion scavenged Fe3+ from the [Fe3+-L1] complex and quenched its fluorescence via its ring-closed spirolactam form. Advanced level molecular logic devices using different inputs (2 and 4 inputs) as advanced level logic gates and memory devices were constructed. The large enhancement in fluorescence emission of L1 upon complexation with M3+ metal ions makes the probe suitable for the bio-imaging of M3+ (M = Fe, Al and Cr) in living cells.

Magnetic performance and defect characterization studies of core-shell architectured MgFe2O4@BaTiO3 multiferroic nanostructures.

Multiferroics that permit manipulation of the magnetization vector exclusively by electric fields have spawned extensive interest for memory and logic device applications. In line with this understanding, we herein report the encapsulation of non-ferroelectric magnesium ferrite (MgFe2O4) nanoparticles in a ferroelectric shell of BaTiO3 to produce a system with engineered dielectric, magnetic, magneto-electric and ferroelectric properties. The interface effect on the strain transfer was observed to strongly influence the magneto-electric coupling and the electric and magnetic properties of the system. The model polyhedral image of MgFe2O4@BaTiO3 has helped to get an insight into the core-shell structure. The multiferroicity induced by the excellent coupling between the ferroelectric and magnetostrictive phases at the core-shell interface unlocks wide prospects for device downscaling and information storage applications. The influence of magnetostrictive stress on the magneto-electric coupling effects and domain dynamics was further studied using transmission electron microscopy (TEM) and atomic force microscopy images. Interestingly, the realization of a superparamagnetic multiferroic system has been a breakthrough and facilitates ultra high density magnetic data storage technologies. Evidence for spontaneous polarization and the ferroelectric trait exhibited by the multiferroic samples was revealed from the P-E hysteresis loop. The investigation of defect evolution in the system was carried out using positron annihilation lifetime spectroscopy (PALS) and coincidence Doppler broadening spectroscopy (CDBS) of annihilation radiation and the studies revealed thermal diffusion of positrons into the interfacial regions within the core-shell structure and the "formation and pick-off annihilation of orthopositronium atoms". It is concluded that interface engineering is a strong means for manipulation of the magnetic, dielectric and magneto-electric properties in multiferroic heterostructures for high density electrical energy and magnetic data storage.

The toxicity of antiprion antibodies is mediated by the flexible tail of the prion protein.

Prion infections cause lethal neurodegeneration. This process requires the cellular prion protein (PrP(C); ref. 1), which contains a globular domain hinged to a long amino-proximal flexible tail. Here we describe rapid neurotoxicity in mice and cerebellar organotypic cultured slices exposed to ligands targeting the α1 and α3 helices of the PrP(C) globular domain. Ligands included seven distinct monoclonal antibodies, monovalent Fab1 fragments and recombinant single-chain variable fragment miniantibodies. Similar to prion infections, the toxicity of globular domain ligands required neuronal PrP(C), was exacerbated by PrP(C) overexpression, was associated with calpain activation and was antagonized by calpain inhibitors. Neurodegeneration was accompanied by a burst of reactive oxygen species, and was suppressed by antioxidants. Furthermore, genetic ablation of the superoxide-producing enzyme NOX2 (also known as CYBB) protected mice from globular domain ligand toxicity. We also found that neurotoxicity was prevented by deletions of the octapeptide repeats within the flexible tail. These deletions did not appreciably compromise globular domain antibody binding, suggesting that the flexible tail is required to transmit toxic signals that originate from the globular domain and trigger oxidative stress and calpain activation. Supporting this view, various octapeptide ligands were not only innocuous to both cerebellar organotypic cultured slices and mice, but also prevented the toxicity of globular domain ligands while not interfering with their binding. We conclude that PrP(C) consists of two functionally distinct modules, with the globular domain and the flexible tail exerting regulatory and executive functions, respectively. Octapeptide ligands also prolonged the life of mice expressing the toxic PrP(C) mutant, PrP(Δ94-134), indicating that the flexible tail mediates toxicity in two distinct PrP(C)-related conditions. Flexible tail-mediated toxicity may conceivably play a role in further prion pathologies, such as familial Creutzfeldt-Jakob disease in humans bearing supernumerary octapeptides.

Immunohistochemistry on pattern of ocular & adnexal tumours in a tertiary eye care centre of Northeast India.

BACKGROUND & OBJECTIVES: Ocular and adnexal tumours are important causes of morbidity in India and globally. Immunohistochemistry (IHC) is a vital molecular pathology tool, which helps to diagnose a tumour with more accuracy. The present study was undertaken to document the profile of ocular and adnexal tumour with IHC at a tertiary eye care center in Northeast India. METHODS: This was a prospective and laboratory-based study. Histopathological and IHC study of the ocular and adnexal tumour was carried out from 2012 to 2014. Selection of pathological cases was made on the result of the histological diagnosis. All samples were subjected to IHC using kits for different antibodies as per indications. RESULTS: In total, 645 tumours were included in our study, with 449 benign conditions and 196 were malignant tumours. Total IHCs were done in 87 tumours and 238 of antibodies were used. Non-Hodgkin's lymphomas (B-cell, low-to-intermediate type and mucosal-associated lymphoid tumours) were the most common tumor. INTERPRETATION & CONCLUSIONS: Clinical utility of the IHCs in different ophthalmic tumours can enable pathologists to make an accurate diagnosis and thus help in the overall management of the patient care. IHC may be carried out using various methods and some of the methods practiced are time consuming and tedious. In this study, kit methods were used which were found to be simpler and less time-consuming.

Overviews of Biomimetic Medical Materials.

This chapter describes the overviews of biomimetic medical materials which covers innovation and significance of terminology, diverse fabrication methods, and technologies ranges from nanotechnology to 3D printing to develop biomimetic materials for medical applications. It also depicts specific fundamental characteristics required for a material to be a model biomimetic material for particular medical application. It basically outlines current statuses of biomimetic medical materials used for tissue engineering and regenerative medicine, drug/protein delivery, bioimaging, biosensing, and 3D bioprinting technology. It also illustrates the effect of functionalization of a material through chemical and biological approaches towards different applications. Not only, the key properties and potential applications of the biomimetic materials, but it also explains the protection and utilization of intellectual property associated with biomedical materials.

Facile synthesis of hierarchical nickel (III) oxide nanostructure: A synergistic remediating action towards water contaminants.

Heavy metal ion removal from consumable water is an indispensable need to maintain healthy life. Therefore cost effective and highly efficient sorbents are strongly needed to pose threat to real water pollution. Nanomaterials are widely used to maintain clean aqueous system in a very cost effective way with high removal efficiency. In this present work, pure coral like Ni2O3 nanostructures were prescribed for Cr(VI) remediation which were prepared by two step synthesis procedure at room temperature. The single hierarchical morphology as confirmed from HRTEM (size∼200 nm) were subjected to toxic Cr(VI) ion removal experiments. They were found to remove ∼65% Cr(VI) ions that was higher than that of pure Ni2O3 nanoparticles of comparable size. The enhanced properties were explained on the basis of the defect states present within the nanostructure, investigated by positron annihilation lifetime spectroscopy (PALS). It was found that the hierarchical nanostructure had more number of di-vacancies and vacancy-clusters as compared to the particles. On performing isotherm fitting, it was found that the coral like morphology had a high heterogeneity factor that aided to a high adsorption rate when compared to the pure Ni2O3 nanoparticles (which had a homogenous surface). The synthesized nanostructure was severely toxic to bacterial community having minimum inhibitory concentration (MIC) of ∼300 µg/L. Also the nanostructure exhibited dual functionality towards Cr(VI) and bacteria contaminated water at 200 µg/ml. The maximum Cr(VI) removal efficiency for this dual system is found to be 39% whereas antibacterial activity was turned out to be 30% which was extensively higher than that of toxic Cr(VI) ions. A plausible mechanism for the dual functionality was also predicted.

Acute disseminated encephalomyelitis: A clinical and neuroradiological profile of pediatric patients.

OBJECTIVES: To discuss the clinical and neuroradiological profile of pediatric patients with acute disseminated encephalomyelitis (ADEM). DESIGN: Prospective observational study Settings: Children with clinico-radiological diagnosis of ADEM admitted in the pediatric ward of the Institute of Child Health between July 2009 to Sepetember 2014 were included. MATERIALS AND METHODS: Clinical and neuroradiological parameters of children suffering from ADEM were noted. RESULTS: A total of 36 children were included in the study, among whom approximately 50% had a history of either a preceding viral infection or the administration of a vaccination; and, 92% of them presented with some form of neurological deficits. Encephalopathy was present in 92% children at the time of admission. Seizures were present in 42% of children. The cerebrospinal fluid (CSF) study was non-contributory and magnetic resonance imaging (MRI) was diagnostic in most of the cases. The lesions were usually asymmetrically placed. All of them were treated with steroids and had a good prognosis, with complete neurological recovery in 75% of the children. CONCLUSION: Although it is perceived as a rare disease, ADEM is fairly common in the pediatric population, Most often, it is misdiagnosed as a meningoencephalitis. An early neuroradiological identification of the demyelinating lesions and treatment with steroid therapy leads to an excellent outcome.

Efficient production of Tymovirus like particles displaying immunodominant epitopes of Japanese Encephalitis Virus envelope protein.

Japanese Encephalitis (JE) is a mosquito borne arboviral infection caused by Japanese Encephalitis Virus (JEV). It is a major cause of viral encephalitis in Asian countries including India. In the present study, we have used a Tymovirus [i.e. Physalis Mottle Virus (PhMV) coat protein (CP)], which forms virus like particles (VLPs) as a template to display immunodominant epitopes of JEV envelope (E) protein. The immunodominant epitopes of JEV were inserted at the N-terminus of the wild type PhMV CP, and these constructs were cloned and expressed in Escherichia coli. The chimeric proteins were purified from the inclusion bodies and evaluated for VLP formation. The purified protein was identified by Western blotting and VLP formation was studied and confirmed by transmission electron microscopy and dynamic light scattering. Finally, the immunogenicity was studied in mice. Our results indicate that the chimeric protein with JEV epitopes assembled efficiently to form VLPs generating neutralizing antibodies. Hence, we report the purified chimeric VLP would be a potent vaccine candidate, which needs to be evaluated in a mouse challenge model.

Profile of ocular and adnexal tumours at a tertiary institute of northeast India.

PURPOSE: To present the profile of patients with ocular and adnexal tumours presenting at a tertiary eye care institute in northeast India in ten years between 2003 and 2013. DESIGN: Hospital based retrospective review of medical records. METHOD: The clinical history, site of involvement and pathological diagnoses were retrieved from ocular pathology registers from October 2003-October 2013. This included conjunctival, orbital, adnexal and intraocular tumours. All specimens were fixed, processed and stained. Immunohistochemistry was carried out where ever indicated to come to a final diagnosis. RESULTS: In all 1003 cases were included in our study, with 622 (62.01%) benign tumours and 381 (37.98%) malignant tumours. 54.63% were males and 45.36% were females. Amongst the conjunctival tumours, squamous cell carcinoma (SCC) (72.5%) and nevus (39.6%) were the most common malignant and benign tumour, respectively. Non-Hodgkin's lymphoma (NHL) (60%) was the most common malignant orbital tumour. Retinoblastoma (RB) (81.5%) was the most common intraocular malignancy, followed by melanoma (18.4%). Basal cell carcinoma (BCC) (35.1%) was the most common malignancy in the lid. CONCLUSION: NHL and SCC were the most frequently seen malignant tumours in adults while RB was the most common intraocular tumour in children.

A One-Pot Cascade Strategy toward Organocatalytic Enantioselective Construction of Fused Benzimidazoles.

Herein, we describe an asymmetric assembly of ortho-aromatic diamines and formyl tethered Michael acceptors forming chiral fused benzimidazoles. A cinchona-alkaloid-derived bifunctional squaramide catalyst enables the methodology through on-site dihydrobenzimidazole formation followed by an aza-Michael addition/oxidation cascade. This protocol stands out for its excellent catalytic efficiency over the background reaction and its mild conditions, making it more practical. Various Michael acceptors, including enones, ester, and thioester, were successful substrates in this study. Additionally, this methodology has demonstrated scalability and successfully showcased postsynthetic transformations.

Studies on cationic ocular emulsions containing bipartitioned oil droplets to codeliver cyclosporin A and etodolac.

Background: To prepare ocular emulsions containing bipartitioned oil droplets to entrap cyclosporin A (0.05% w/w) and etodolac (0.2% w/w) by using castor, olive and silicon oils. Methods: The physicochemical characterizations of prepared emulsions were performed. The drug's biodistribution profiles and pharmacokinetic parameters from emulsions were checked using the ultraperformance liquid chromatography-tandem mass spectrometry method in the ocular tissues of the healthy rabbit eye model. Results: The emulsions displayed 365.13 ± 7.21 nm size and 26.45 ± 2.09 mV zeta potential. The ferrying of two drugs after releasing from emulsions occurred across corneal/conjunctival tissues to enter the vitreous and sclera following a single drop administration into the rabbit's eyes. Conclusion: The dual drug-loaded emulsions were more likely to produce synergistic anti-inflammatory activity for managing moderate-to-severe dry eye disease.

[Box: see text].

Post-chemotherapy changes in retinal pigment epithelium in retinoblastoma eyes.

OBJECTIVE: Histopathological analysis of the retinal pigment epithelial (RPE) changes in retinoblastoma (RB) cases who received pre-surgical chemotherapy. DESIGN: Laboratory-based observational study. METHODS: Five-year analysis was performed to identify Retinoblastoma cases who underwent enucleation after receiving systemic chemotherapy. Grossly, RPE cells were observed in flat preparation in small calottes by staining with fluorescein stain in the raw specimens. They were documented under the objective of compound microscope and compared with hematoxylin and eosin-stained slides in the permanent tissue sections. RESULTS: Out of 51 cases of RB, post-chemotherapy enucleation was performed in 17 cases. Mean age of enucleation was 3.2 years. Endophytic RB (11 cases, 64.71%) was more common than the exophytic variety. Choroidal involvement was noted in 8 cases (47.06%), and optic nerve involvement was seen in 5 cases (29.4%). Focal and diffuse RPE changes were seen in one case each (5.88%). Central RPE cell changes near the cell nucleus were seen in all 17 cases (100%), which were documented by both fluorescein and Hematoxylin and eosin stain (100%). Drusens were observed in 8 cases (47.06%), and RPE proliferations were seen in 3 cases (17.65%). CONCLUSION: The study highlights the characteristic histopathological RPE changes after systemic chemotherapy in RB cases. These changes may be attributable to cell nucleus damage after chemotherapy.

Enhanced prokaryotic expression of dengue virus envelope protein.

PURPOSE: To highlight the expression and purification of the recombinant dengue virus type-1 antigen exploiting the codon optimized full length envelope for increased yield in E. coli. METHODS: A 6x His tag was inserted at the C terminus to facilitate purification. The purified protein was recognized in Western blot by Monoclonal antibody specific for the tag. The in vitro refolded recombinant protein was used to immunize mice for the development of hybridomas and also analyzed for its biological functionality with heparan sulfate binding assay. RESULTS: The polyclonal anti-sera from the immunized mice were found to recognize the envelope protein thereby establishing the immunogenicity of the protein. CONCLUSION: The purified envelope protein could potentially be used towards dengue diagnostics and vaccine development efforts. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Hydrazine Hydrate in Asymmetric Synthesis: A Bifunctional Squaramide Catalytic Approach toward Fused Pyrazolines.

A unified strategy has been developed to utilize hydrazine hydrate in asymmetric organic synthesis by overcoming the rapid background reaction with dienone. The H-bond donor ability of the cinchona-alkaloid-derived squaramide catalyst unlocks this previously deemed infeasibility. The dissymmetric hydrazine addition to symmetrical dienones tolerates various substitutions, resulting in the formation of optically pure fused pyrazoline derivatives under mild reaction conditions. Furthermore, the scalability of this methodology and a successful demonstration of postsynthetic transformations have been accomplished.

Validation of urinary reproductive hormone measurements using a novel smartphone connected reader.

Home use tests to monitor hormone trends during the menstrual cycle have been available over-the-counter for a long time. However, these tests often depend upon manual readouts and hence may lead to false analysis. Furthermore, a lot of these tests are also not quantitative. The aim of this study was to evaluate the accuracy of the quantitative home-based fertility monitor, Inito Fertility Monitor (IFM) and to use it to identify novel hormone trends in natural menstrual cycles. There were two aspects to our analysis: (i) Evaluating the efficacy of Inito Fertility Monitor in the measurement of urinary Estrone-3-glucuronide (E3G), Pregnanediol glucuronide (PdG) and Luteinizing hormone (LH), and (ii) A retrospective study of patients' hormone profiles using IFM. To evaluate the efficacy, the recovery percentage of the three hormones from IFM was evaluated using standard spiked solutions, the accuracy of measurement was calculated and the correlation between reproducible values from IFM and ELISA was established. During the validation of IFM, novel hormone trends were also observed. In order to reinforce the observations, a second group of 52 women was recruited. Assessment of the accuracy of IFM and evaluation of the volunteer urine samples was performed in a laboratory. Home assessment of hormone analysis was carried out using IFM. For the validation study, 100 women aged 21-45 years with cycle lengths ranging from 21 to 42 days were recruited. The participants had no previously diagnosed infertility conditions and their cycle lengths did not vary for more than 3 days from the expected cycle length. Daily first morning urine samples were collected from these 100 women. For the second group, 52 women were selected meeting the same criteria set for the validation study and IFM was provided to these women for testing at home. Coefficient of variation and recovery percentage of IFM with respect to laboratory based ELISA. Percentage occurrence of novel hormone trends and AUC analysis of a novel criteria identified for confirming ovulation. We observed that with all three hormones, IFM had an accurate recovery percentage. We found that the assay has an average CV of 5.05% in PdG measurement, 4.95% in E3G measurement and 5.57% in LH measurement. Furthermore, in predicting the concentration of E3G, PdG and LH in urine samples, we show that IFM has a high correlation with ELISA. In this study, we could also reproduce hormones trends across the menstrual cycle that have been observed by previous studies. We also identified a novel criterion for earlier confirmation of ovulation which could accurately distinguish ovulatory from anovulatory cycles with 100% specificity and had an area under the ROC curve of 0.98. In addition, we identified a new hormone trend which could be observed in 94.5% of the ovulatory cycles. The Inito Fertility Monitor is an effective tool for calculating the urinary concentrations of E3G, PdG and LH and can also be used to provide accurate fertility scores and confirm ovulation. We show that certain hormone trends associated with urinary E3G, PdG and LH could be accurately captured using IFM. In addition, we report a novel criterion for earlier confirmation of ovulation compared to existing criteria. Finally, we present a novel hormone pattern associated with most of the menstrual cycles by examining hormone profiles from the volunteers recruited for the clinical trial.Trial registration: The trial is registered at the current controlled trials ISRCTN registry #ISRCTN15534557.

Predicting serum hormone concentration by estimation of urinary hormones through a home-use device.

STUDY QUESTION: Can a home-use device be used to predict serum hormone levels? SUMMARY ANSWER: A home-use device can predict urinary hormone values which are well-correlated to serum concentrations of respective hormones and hence can be used as a proxy for serum measurements. WHAT IS KNOWN ALREADY: Home-use devices that predict ovulation are calibrated against the actual day of ovulation. However, the correlation of any quantitative system to serum hormone concentrations has not been established. STUDY DESIGN SIZE DURATION: A total of 73 data points obtained from 20 participants across different phases of the menstrual cycle, i.e. bleeding days, follicular phase and luteal phase were used to establish the correlation between serum hormones and urinary metabolite values. Single data points from 20 random users were used to assess the correlation established. PARTICIPANTS/MATERIALS SETTING METHODS: Participants were women in the fertile age groups and only current users of the home-use device. Selection was done based on inclusion and exclusion criteria. Blood hormones were tested using chemiluminescent immunoassays and urinary measurements were taken on the home-use device at home. MAIN RESULTS AND THE ROLE OF CHANCE: Serum estradiol (E2), progesterone (P4) and LH were correlated with urinary estrone-3-glucuronide (E3G), pregnanediol glucuronide (PdG) and LH with an R 2 of 0.96, 0.95 and 0.98, respectively. Repredicted serum concentration obtained by using the correlation equation had a correlation of 0.92, 0.94 and 0.93 in unknown samples. LIMITATIONS REASONS FOR CAUTION: The study was designed to include women who have normal cycle lengths regularly; therefore, the values obtained were in the normal range. Certain infertility conditions may cause the values to be higher and correlation in such cases needs to be established. WIDER IMPLICATIONS OF THE FINDINGS: The results of this study imply a new tool that can be used by fertility specialists as a proxy for blood tests whenever required. Extended study on this system can enable its use in assisted reproductive techniques as well. STUDY FUNDING/COMPETING INTERESTS: No funding was received for this study. S.P. and D.D. are employees of the research and development division of Samplytics Technologies Pvt. Ltd. which is a forwarder for Inito Inc., USA. A.R. and V.A.V. are co-founders of Inito Inc., USA. TRIAL REGISTRATION NUMBER: The trial was registered at the International Standard Randomised Controlled Trial Number (ISRCTN) registry (Identifier: ISRCTN15534557).