MicroRNA-125b regulates vitamin D resistance by targeting CYP24A1 in the progression of gestational diabetes mellitus.

Vitamin D deficiency is prevalent in pregnancy and has been associated with increased occurrences of preeclampsia, cesarean delivery, neonatal bacterial vaginosis, and gestational diabetes. CYP24A1, recognized as a key factor in vitamin D metabolism homeostasis, encodes 24-hydroxylase responsible for converting 25(OH)D3 and 1,25(OH)2D3 into inactive metabolites. Recently, we have reported CYP24A1 overexpression in patients with gestational diabetes mellitus (GDM) and trophoblast cells exposed to hyperglycemia. In this study, we explored miRNA-mediated regulation of CYP24A1 in GDM progression, validating our findings through silencing experiments in a trophoblast cell line. In silico tools identified miR-125b-5p as a putative target of CYP24A1. Expression analysis revealed downregulation of miR-125b-5p in blood samples from early GDM and GDM compared to healthy pregnant women, positively correlating with vitamin D levels. Hyperglycemic exposure in human trophoblastic cell lines (BeWo) decreased miR-125b-5p expression, concomitant with an increase in CYP24A1. To confirm the regulatory role of miR-125b on CYP24A1, we transfected BeWo cells with antimiR-125b or miR-125b mimic. AntimiR-125b transfection heightened CYP24A1 levels, while miR-125b mimic overexpression resulted in decreased CYP24A1 expression. These findings establish miR-125b as a regulator of CYP24A1. To explore the influence of miR-125b on vitamin D metabolism, trophoblast cells overexpressing miR-125b were treated with 0.1 and 1 µM calcitriol. Hyperglycemic conditions exhibited a reduction in CYP24A1 levels. Collectively, our results indicate that miR-125b may regulate vitamin D metabolism by targeting CYP24A1, contributing to GDM progression. These findings may pave the way for understanding vitamin D resistance in concurrent GDM development and identifying novel miRNAs targeting CYP24A1.

Impact of vitamin D resistance genes on vitamin D deficiency during pregnancy among the South Indian population.

Increasing evidence suggests that vitamin D (Vit-D) could be pivotal in maintaining normal glucose homeostasis. Low levels of Vit-D in early pregnancy are associated with a higher risk of gestational diabetes mellitus (GDM). Though several reports have highlighted the prevalence of vit-D deficiency among pregnant women, its underlying cause has not yet been fully elucidated. In this connection, a few studies have found the development of resistance to Vit-D, including the levels of Vitamin D receptor (VDR) and transcription regulators that modify VDR action, as well as the bioavailability of Vit-D. We aimed to determine the levels of Vit-D resistance genes such as 25-HydroxyVit-D-24-hydroxylase (CYP24A1), VDR repressor genes (SNAIL and SMRT) and their association between Vit-D concentrations in early pregnancy, and the risk of gestational diabetes mellitus (GDM). A prospective observational study was conducted on healthy pregnant women (NGDM; n = 50) and GDM (n = 50) attending routine antenatal care at SRM Medical College Hospital, Chennai, recruited at 12 weeks of gestation. We found that the serum levels of Vit-D were low in GDM subjects and negatively correlated with the fasting glucose levels. Further, increased expressions of Vit-D resistance genes such as CYP24A1, SNAIL, and SMRT were observed in GDM subjects and negatively correlated with the serum levels of Vit-D. Furthermore, we have validated the data using the trophoblast cell line, BeWo, exposed to calcitriol under a hyperglycemic environment. Our finding showed that increased expression of Vit-D resistance genes in pregnancy may be associated with a greater risk of adverse pregnancy outcomes, including GDM.

C-band operating plasmonic sensor with a high Q-factor/figure of merit based on a silicon nano-ring.

In this paper, we take advantage of the high refractive index property of silicon to design a practical and sensitive plasmonic sensor on a photonic integrated circuit (PIC) platform. It has been demonstrated that a label-free refractive index sensor with sensitivity up to 1124 nm/RIU can be obtained using a simple design of a silicon nano-ring with a concentric hexagonal plasmonic cavity. It has also been shown that, with optimum structural parameters, a quality factor (Q-factor) of 307 and a figure of merit (FOM) of 234R I U -1 can be achieved, which are approximately 8 times and 5 times higher than the proposed sensors counterparts, respectively. In addition, the resonance mode of the hexagonal cavity with Si nano-ring (HCS) sensor can be adjusted to operate in the C-band, which is a highly desirable wavelength range in terms of compatibility with devices in PIC technology.

Old versus new antihistamines: Effects on cognition and psychomotor functions.

Context: Antihistamines (AHs) are the most widely long-term therapeutic option to manage allergic diseases. This research aimed to study the effects of long-term administration of AHs: on cognitive (memory, mood, attention, sleep and executive function) and psychomotor performance. Materials and Methods: This prospective, observational study for a total duration of 30 months was carried out at the Dermatology OPD in adult patients with dermatological condition who were newly prescribed either chlorpheniramine (4 mg, BD), levocetirizine (10 mg, OD), fexofenadine (180 mg, OD) or bepotastine (10 mg, BD) for at least 28 days as per inclusion and exclusion criteria after taking written informed consent. A detailed history of the patients, memory (using PGI memory scale) and psychomotor functions, Brief Mood Introspection Scale and Epworth Sleepiness Scale were assessed at baseline, 1 week and 4 weeks. Data obtained were analysed using paired sample t-test and one-way ANOVA followed by post hoc analysis (P-value <0.05 statistically significant). Results: A total of 22 in chlorpheniramine group, 23 in levocetirizine group, 20 in fexofenadine group and 18 in bepotastine group were analysed. Chlorpheniramine and levocetirizine had deteriorating effects on cognitive and psychomotor performance, whereas fexofenadine and bepotastine showed positive effect on various cognitive and psychometric tasks. The study results showed chlorpheniramine and levocetirizine to be having sedative effects, whereas fexofenadine was nonsedating. In bepotastine group, no effect on sleep was observed. No significant difference in mood scores was observed in between chlorpheniramine, levocetirizine and fexofenadine groups. In bepotastine group, arousal calm and positive tired scores increased at 4 week as compared to baseline. Conclusion: Patients with dermatological illnesses can be prescribed fexofenedine and bepotastine, as compared to chlorpheniramine and levocetirizine, and their cognitive and psychological functions should be evaluated periodically with suitable tests.

High spectro-temporal compression on a nonlinear CMOS-chip.

Optical pulses are fundamentally defined by their temporal and spectral properties. The ability to control pulse properties allows practitioners to efficiently leverage them for advanced metrology, high speed optical communications and attosecond science. Here, we report 11× temporal compression of 5.8 ps pulses to 0.55 ps using a low power of 13.3 W. The result is accompanied by a significant increase in the pulse peak power by 9.4×. These results represent the strongest temporal compression demonstrated to date on a complementary metal-oxide-semiconductor (CMOS) chip. In addition, we report the first demonstration of on-chip spectral compression, 3.0× spectral compression of 480 fs pulses, importantly while preserving the pulse energy. The strong compression achieved at low powers harnesses advanced on-chip device design, and the strong nonlinear properties of backend-CMOS compatible ultra-silicon-rich nitride, which possesses absence of two-photon absorption and 500× larger nonlinear parameter than in stoichiometric silicon nitride waveguides. The demonstrated work introduces an important new paradigm for spectro-temporal compression of optical pulses toward turn-key, on-chip integrated systems for all-optical pulse control.

Controlling Magnetic Anisotropy in a Zero-Dimensional S = 1 Magnet Using Isotropic Cation Substitution.

The [Zn1-xNix(HF2)(pyz)2]SbF6 (x = 0.2; pyz = pyrazine) solid solution exhibits a zero-field splitting (D) that is 22% larger [D = 16.2(2) K (11.3(2) cm-1)] than that observed in the x = 1 material [D = 13.3(1) K (9.2(1) cm-1)]. The substantial change in D is accomplished by an anisotropic lattice expansion in the MN4 (M = Zn or Ni) plane, wherein the increased concentration of isotropic Zn(II) ions induces a nonlinear variation in M-F and M-N bond lengths. In this, we exploit the relative donor atom hardness, where M-F and M-N form strong ionic and weak coordinate covalent bonds, respectively, the latter being more sensitive to substitution of Ni by the slightly larger Zn(II) ion. In this way, we are able to tune the single-ion anisotropy of a magnetic lattice site by Zn-substitution on nearby sites. This effect has possible applications in the field of single-ion magnets and the design of other molecule-based magnetic systems.

Pre-locus coeruleus neurons in rat and mouse.

Previously, we identified a population of neurons in the hindbrain tegmentum, bordering the locus coeruleus (LC). We named this population the pre-locus coeruleus (pre-LC) because in rats its neurons lie immediately rostral to the LC. In mice, however, pre-LC and LC neurons intermingle, making them difficult to distinguish. Here, we use molecular markers and anterograde tracing to clarify the location and distribution of pre-LC neurons in mice, relative to rats. First, we colocalized the transcription factor FoxP2 with the activity marker Fos to identify pre-LC neurons in sodium-deprived rats and show their distribution relative to surrounding catecholaminergic and cholinergic neurons. Next, we used sodium depletion and chemogenetic activation of the aldosterone-sensitive HSD2 neurons in the nucleus of the solitary tract (NTS) to identify the homologous population of pre-LC neurons in mice, along with a related population in the central lateral parabrachial nucleus. Using Cre-reporter mice for Pdyn, we confirmed that most of these sodium-depletion-activated neurons are dynorphinergic. Finally, after confirming that these neurons receive excitatory input from the NTS and paraventricular hypothalamic nucleus, plus convergent input from the inhibitory AgRP neurons in the arcuate hypothalamic nucleus, we identify a major, direct input projection from the medial prefrontal cortex. This new information on the location, distribution, and input to pre-LC neurons provides a neuroanatomical foundation for cell-type-specific investigation of their properties and functions in mice. Pre-LC neurons likely integrate homeostatic information from the brainstem and hypothalamus with limbic, contextual information from the cerebral cortex to influence ingestive behavior.

Single-Element Diffraction-Limited Fisheye Metalens.

Wide field-of-view (FOV) optical functionality is crucial for implementation of advanced imaging and image projection devices. Conventionally, wide FOV operation is attained with complicated assembly of multiple optical elements known as "fisheye lenses". Here we present a novel metalens design capable of performing diffraction-limited focusing and imaging over an unprecedented near 180° angular FOV. The lens is monolithically integrated on a one-piece flat substrate and involves only a single layer of metasurface that corrects third-order Seidel aberrations including coma, astigmatism, and field curvature. The metalens further features a planar focal surface, which enables considerably simplified system architectures for applications in imaging and projection. We fabricated the metalens using Huygens meta-atoms operating at 5.2 µm wavelength and experimentally demonstrated aberration-free focusing and imaging over the entire FOV. The design concept is generic and can be readily adapted to different meta-atom geometries and wavelength ranges to meet diverse application demands.

Assessment of basal implants in compromised ridges.

AIM: The aim of the present study was to evaluate clinically, radiographically, and functionally the outcomes of immediately loaded basal implants when placed in patients with compromised bone/alveolar ridges. MATERIALS AND METHODS: A total of 18 systemically healthy (9 male and 9 female) subjects with compromised bone with poor quantity or quality were included in the study. A total number of 57 implants was placed, out of which 26 implants were placed in maxilla and 31 implants in mandible. There were 6 patients in which single implants were placed and in rest of the 12 patients, multiple implants were placed, out of which full mouth rehabilitation was done in one patient. In 10 patients, implants were placed immediately in fresh extraction socket and in 7 patients, implants were placed in healed edentulous site. In all the patients, loading was done immediately within 72 h of implant placement. All patients were evaluated for primary and secondary stability, pain, periimplant bone levels using IOPA with grid and CBCT, bleeding, suppuration, sulcular bleeding index, prosthetic complications, and patient satisfaction at specified time intervals. RESULT: All the values obtained during the study were expressed in the form of mean, standard deviation, and standard error of the mean. The parameters were compared between groups using Paired t-test for intragroup comparison at a similar time, i.e., baseline, 1 month, and 3 months. The data collected was comprehensively analyzed using SPSS software. All implants were successful, with no incidence of infection, nil mobility at the end of the study period of 6 months. CONCLUSION: Thus, it can be concluded from the present study, that Basal implants can play a vital role in the rehabilitation of patients, where compromised quality and/or quantity of bone is present and additional augmentation procedures would be required for the placement of conventional root form implants.

Dynamic Complex Emulsions as Amplifiers for On-Chip Photonic Cavity-Enhanced Resonators.

Despite the recent emergence of microcavity resonators as label-free biological and chemical sensors, practical applications still require simple and robust methods to impart chemical selectivity and reduce the cost of fabrication. We introduce the use of hydrocarbon-in-fluorocarbon-in-water (HC/FC/W) double emulsions as a liquid top cladding that expands the versatility of optical resonators as chemical sensors. The all-liquid complex emulsions are tunable droplets that undergo dynamic and reversible morphological transformations in response to a change in the chemical environment (e.g., exposure to targeted analytes). This chemical-morphological coupling drastically modifies the effective refractive index, allowing the complex emulsions to act as a chemical transducer and signal amplifier. We detect this large change in the refractive index by tracking the shift of the enveloped resonant spectrum of a silicon nitride (Si3N4) racetrack resonator-based sensor, which correlates well with a change in the morphology of the complex droplets. This combination of soft materials (dynamic complex emulsions) and hard materials (on-chip resonators) provides a unique platform for liquid-phase, real-time, and continuous detection of chemicals and biomolecules for miniaturized and remote, environmental, medical, and wearable sensing applications.

An analysis of the use of antimicrobial agents in outdoor patients of ophthalmology.

OBJECTIVES: The study was aimed to analyze commonly used antimicrobials in outdoor patients of ophthalmology department. MATERIALS AND METHODS: The study was an observational, cross-sectional study carried out in the Department of Pharmacology and Ophthalmology after approval from the head of departments and Institutional Ethics Committee. All the patients age 18 years and above who were prescribed antimicrobials and gave consent were included in study. Data were recorded in a case study form containing relevant patient information and results of general, ocular, and special examinations along with the details of antimicrobials prescribed. Data were analyzed according to the World Health Organization/International Network for Rational Use of Drugs indicators and appropriate statistical tests. RESULTS: A total of 900 patients who were prescribed antimicrobial agents (AMAs) were included in the study. The most common chief complaint was diminution of vision (25.78%). The most common indication of use of AMAs was for treating ocular infections (50.22%). The most commonly prescribed antimicrobial group was fluoroquinolone (FQ) (63.8%) and the most common drug was moxifloxacin (35.95%). The most common dosage form of AMAs was eye drops (68.55%). The average number of drugs per encounter was 4.41. The percentage of encounters with injectables prescribed was 0.67%. The percentage of use of antibiotics was 100%. The percentage of total drugs and AMAs prescribed by generic name was 41.5 and 11.92, respectively. The percentage of antimicrobial drugs prescribed from essential drugs list was 34.24%. The mean duration of antimicrobial therapy was 7.2 ± 4.54 days. CONCLUSION: More than half of the patients are prescribed multiple AMAs. Moxifloxacin, a newer generation FQ , was the most commonly prescribed AMA in our study. Educational interventions and strict adherence to hospital antimicrobial use policy are needed to restrict the use of AMAs and increase rational prescribing.

CONVERGENCE PROPERTIES OF ADAPTIVE SYSTEMS AND THE DEFINITION OF EXPONENTIAL STABILITY.

The convergence properties of adaptive systems in terms of excitation conditions on the regressor vector are well known. With persistent excitation of the regressor vector in model reference adaptive control the state error and the adaptation error are globally exponentially stable or, equivalently, exponentially stable in the large. When the excitation condition, however, is imposed on the reference input or the reference model state, it is often incorrectly concluded that the persistent excitation in those signals also implies exponential stability in the large. The definition of persistent excitation is revisited so as to address some possible confusion in the adaptive control literature. It is then shown that persistent excitation of the reference model only implies local persistent excitation (weak persistent excitation). Weak persistent excitation of the regressor is still sufficient for uniform asymptotic stability in the large, but not exponential stability in the large. We show that there exists an infinite region in the state-space of adaptive systems where the state rate is bounded. This infinite region with finite rate of convergence is shown to exist not only in classic open-loop reference model adaptive systems but also in a new class of closed-loop reference model adaptive systems.

Dissection of Human Retina and RPE-Choroid for Proteomic Analysis.

The human retina is composed of the sensory neuroretina and the underlying retinal pigmented epithelium (RPE), which is firmly complexed to the vascular choroid layer. Different regions of the retina are anatomically and molecularly distinct, facilitating unique functions and demonstrating differential susceptibility to disease. Proteomic analysis of each of these regions and layers can provide vital insights into the molecular process of many diseases, including Age-Related Macular Degeneration (AMD), diabetes mellitus, and glaucoma. However, separation of retinal regions and layers is essential before quantitative proteomic analysis can be accomplished. Here, we describe a method for dissection and collection of the foveal, macular, and peripheral retinal regions and underlying RPE-choroid complex, involving regional punch biopsies and manual removal of tissue layers from a human eye.One-dimensional SDS-PAGE as well as downstream proteomic analysis, such as liquid chromatography-tandem mass spectrometry (LC-MS/MS), can be used to identify proteins in each dissected retinal layer, revealing molecular biomarkers for retinal disease.

Loss reduction of silicon-on-insulator waveguides for deep mid-infrared applications.

We report that propagation loss of optical waveguides based on a silicon-on-insulator (SOI) material platform can be greatly reduced. Our simulations show that the loss, including SiO2 absorption and substrate leakage, but no scattering loss, is 0.024 and 0.53 dB/cm in the deep mid-infrared at 4.8 and 7.1 µm wavelengths, where the material absorption in SiO2 is 100 and 1000 dB/cm, respectively. The loss becomes negligible, compared to scattering loss in Si waveguides. This is enabled by using the TE10 mode in a pedestal waveguide. We also show that the TE10 mode can be excited in the proposed waveguide by the fundamental mode with a coupling efficiency of >94%. Low propagation loss, high coupling efficiency, and fabrication-friendly design would make it promising for practical use of SOI devices in the deep mid-infrared.

Mid-IR supercontinuum generated in low-dispersion Ge-on-Si waveguides pumped by sub-ps pulses.

Ge-on-Si is an attractive material platform for mid-IR broadband sources on a chip because of its wide transparency window, high Kerr nonlinearity and CMOS compatibility. We present a low-loss Ge-on-Si waveguide with flat and low dispersion from 3 to 11 µm, which enables a coherent supercontinuum from 2 to 12 µm, generated using a sub-ps pulsed pump. We show that 700-fs pump pulses with a low peak power of 400 W are needed to generate such a wide supercontinuum, and the waveguide length is around 5.35 mm.

Gamma radiation effects in amorphous silicon and silicon nitride photonic devices.

Understanding radiation damage is of significant importance for devices operating in radiation-harsh environments. In this Letter, we present a systematic study on gamma radiation effects in amorphous silicon and silicon nitride guided wave devices. It is found that gamma radiation increases the waveguide modal effective indices by as much as 4×10-3 in amorphous silicon and 5×10-4 in silicon nitride at 10 Mrad dose. This Letter further reveals that surface oxidation and radiation-induced densification account for the observed index change.

Nonlinear characterization of GeSbS chalcogenide glass waveguides.

GeSbS ridge waveguides have recently been demonstrated as a promising mid - infrared platform for integrated waveguide - based chemical sensing and photodetection. To date, their nonlinear optical properties remain relatively unexplored. In this paper, we characterize the nonlinear optical properties of GeSbS glasses, and show negligible nonlinear losses at 1.55 µm. Using self - phase modulation experiments, we characterize a waveguide nonlinear parameter of 7 W-1/m and nonlinear refractive index of 3.71 × 10-18 m2/W. GeSbS waveguides are used to generate supercontinuum from 1280 nm to 2120 nm at the -30 dB level. The spectrum expands along the red shifted side of the spectrum faster than on the blue shifted side, facilitated by cascaded stimulated Raman scattering arising from the large Raman gain of chalcogenides. Fourier transform infrared spectroscopic measurements show that these glasses are optically transparent up to 25 µm, making them useful for short - wave to long - wave infrared applications in both linear and nonlinear optics.

Gamma radiation effects on silicon photonic waveguides.

To support the use of integrated photonics in harsh environments, such as outer space, the hardness threshold to high-energy radiation must be established. Here, we investigate the effects of gamma (γ) rays, with energy in the MeV-range, on silicon photonic waveguides. By irradiation of high-quality factor amorphous silicon core resonators, we measure the impact of γ rays on the materials incorporated in our waveguide system, namely amorphous silicon, silicon dioxide, and polymer. While we show the robustness of amorphous silicon and silicon dioxide up to an absorbed dose of 15 Mrad, more than 100× higher than previous reports on crystalline silicon, polymer materials exhibit changes with doses as low as 1 Mrad.

Application of Smart Infrastructure Systems approach to precision medicine.

All biological variation is hierarchically organized dynamic network system of genomic components, organelles, cells, tissues, organs, individuals, families, populations and metapopulations. Individuals are axial in this hierarchy, as they represent antecedent, attendant and anticipated aspects of health, disease, evolution and medical care. Humans show individual specific genetic and clinical features such as complexity, cooperation, resilience, robustness, vulnerability, self-organization, latent and emergent behavior during their development, growth and senescence. Accurate collection, measurement, organization and analyses of individual specific data, embedded at all stratified levels of biological, demographic and cultural diversity - the big data - is necessary to make informed decisions on health, disease and longevity; which is a central theme of precision medicine initiative (PMI). This initiative also calls for the development of novel analytical approaches to handle complex multidimensional data. Here we suggest the application of Smart Infrastructure Systems (SIS) approach to accomplish some of the goals set forth by the PMI on the premise that biological systems and the SIS share many common features. The latter has been successfully employed in managing complex networks of non-linear adaptive controls, commonly encountered in smart engineering systems. We highlight their concordance and discuss the utility of the SIS approach in precision medicine programs.

Nonlinear conversion efficiency in Kerr frequency comb generation.

We analytically and numerically investigate the nonlinear conversion efficiency in ring microresonator-based mode-locked frequency combs under different dispersion conditions. Efficiency is defined as the ratio of the average round trip energy values for the generated pulse(s) to the input pump light. We find that the efficiency degrades with growth of the comb spectral width and is inversely proportional to the number of comb lines. It depends on the cold-cavity properties of a microresonator only and can be improved by increasing the coupling coefficient. Also, it can be increased in the multi-soliton state.