Laser-assisted synthesis of nano-hydroxyapatite and functionalization with bone active molecules for bone regeneration.

The main goal of bone tissue engineering research is to replace the allogenic and autologous bone graft substitutes that can promote bone repair. Owing to excellent biocompatibility and osteoconductivity, hydroxyapatite is in extensive research and high demand for both medical and non-medical applications. Although various methods have been developed for the synthesis of hydroxyapatite, in the present study we have shown the use of nanosecond laser energy in the wet precipitation method of nano-hydroxyapatite (nHAP) synthesis without using ammonium solution or any other chemicals for pH maintenance. Here, the present study aimed to fabricate the nanohydroxyapatite using a nanosecond laser. The X-ray diffraction and Fourier transform infrared spectroscopy have confirmed the hydroxyapatite formation under laser irradiation in less time without aging. A transmission electron microscopy confirmed the nano size of synthesized nHAP, which is comparable to conventional nHAP. The length and width of the laser-assisted nHAP were found to be in the range of 50-200 nm and 15-20 nm, respectively, at various laser parameters. The crystallite size obtained by Debye Scherrer formulae was found to be in the range of ∼ 16-36 nm. In addition, laser-assisted nHAP based composite cryogel (nanohydroxyapatite/gelatin/collagen I) was synthesized and impregnated with bioactive molecules (bone morphogenic protein and zoledronic acid) that demonstrated significant osteogenic potential both in vitro in cell experiment and in vivo rat muscle pouch model (abdomen and tibia muscles). Dual-energy X-ray analysis, micro-CT, and histological analysis confirmed ectopic bone regeneration. Micro-CT based histomorphometry showed a higher amount (more than 10-fold) of mineralization for animal groups implanted with composite cryogels loaded with bioactive molecules compared to only composite cryogels groups. Our findings thus demonstrate a controlled and rapid synthetic method for the synthesis of nHAP with various physical, chemical, and biological properties exhibited as comparable to conventionally synthesized nHAP.

Surface-Modified Diopside-Reinforced PCL Biopolymer Composites with Enhanced Interfacial Strength and Mechanical Properties for Orthopedic Applications.

The phase separation of ceramics in a biopolymer matrix makes it challenging to achieve satisfactory mechanical properties required for orthopedic applications. It has been found that silane coupling agents can modify the surface of the bioceramic phase by forming a molecular bridge between the polymer and the ceramic, resulting in improved interfacial strength and adhesion. Therefore, in the present study, silane-modified diopside (DI) ceramic and ε-polycaprolactone (PCL) biopolymer composites were fabricated by injection molding method. The silane modification of DI resulted in their uniform dispersion in the PCL matrix, whereas agglomeration was found in composites containing unmodified DI. The thermal stability of the silane-modified DI-containing composites also increased. The Young's modulus of the composite containing 50% w/w DI modified by 3% w/w silane increased by 103% compared to composites containing 50% w/w unmodified DI. The biodegradation of the unmodified composites was significantly high, indicating their weak interfacial strength with the PCL matrix (p ≤ 0.001). The osteoconductive behavior of the composites was also validated by in vitro cell-material studies. Overall, our findings supported that the silane-modified composites have improved surface roughness, mechanical, and osteoconductive properties compared to the unmodified composite and have the potential for orthopedic applications.

Establishing the Callus-Based Isolation of Extracellular Vesicles from Cissus quadrangularis and Elucidating Their Role in Osteogenic Differentiation.

Extracellular vesicles (EVs) are nano-sized vehicles secreted by all live cells to establish communication with adjacent cells. In recent years, mammalian EVs (MEVs) have been widely investigated for their therapeutic implications in human disease conditions. As the understanding of MEV composition and nature is advancing, scientists are constantly exploring alternatives for EV production with similar therapeutic potential. Plant-derived exosome-like nanovesicles (PDEVs) may be a better substitute for MEVs because of their widespread sources, cost-effectiveness, and ease of access. Cissus quadrangularis (CQ), known as "bone setter or Hadjod", is a perennial plant utilized for its osteogenic potential. Its crude powder extract formulations are widely used as tablets and syrups. The present work elucidates the isolation of exosome-like nanovesicles (henceforth exosomes) from the culture supernatants of an in vitro cultured callus tissue derived from CQ. The physical and biological properties of the exosomes were successfully investigated using different characterization techniques. The therapeutic potential of the CQ exosomes was found to ameliorate the wound scratch injury and oxidative stress conditions in human-derived mesenchymal stem cells (hMSCs) and the pre-osteoblast (MC3T3) cell line. These exosomes also induced the proliferation and differentiation of hMSCs, as observed by alkaline phosphatase activity. These findings may serve as a proof of concept for further investigating the CQ exosomes as a nanocarrier for drug molecules in various therapeutic bone applications.

Biofunctionalization with Cissus quadrangularis phytobioactives accentuates Nano-Hydroxyapatite based ceramic Nano-Cement for Neo-Bone formation in critical sized bone defect.

Developing biofunctionalized ceramic bone substitutes with phytobioactives for their sustained delivery is highly desired to enhance the osteo-active potential of ceramic bone substitutes, reduce the systemic toxicity of synthetic drugs, and increase the bioavailability of phytobioactives. The present work highlights the local delivery of phytobioactives of Cissus quadrangularis (CQ) through nano-hydroxyapatite (nHAP) based ceramic nano-cement. The phytoconstituent profiling represented the optimized CQ fraction to be rich in osteogenic polyphenols and flavonoids like quercetin, resveratrol, and their glucosides. Further, CQ phytobioactives-based formulation was biocompatible, increased bone formation, calcium deposition, proliferation, and migration of cells with simultaneous alleviation of cellular oxidative stress. In the in vivo critical-sized bone defect model, enhanced formation of highly mineralized tissue (BV mm3) in CQ phytobioactives functionalized nano-cement (10.5 ± 2 mm3) were observed compared to the control group (6.5 ± 1.2 mm3). Moreover, the addition of CQ phytobioactives to the bone nano-cement increased the fractional bone volume (BV/TV%) to 21 ± 4.2% compared to 13.1 ± 2.5% in non-functionalized nano-cement. The results demonstrated nHAP-based nano-cement as a carrier for phytobioactives which could be a promising approach for neo-bone formation in different bone defect conditions.

Correlates of post-partum intra-uterine copper-T devices (PPIUCD) acceptance and retention: an observational study from North India.

BACKGROUND: Postpartum intrauterine contraceptives device (PPIUCD) offers an effective means of providing contraceptive services to women in countries with high rates of unmet needs for family planning services. However, scientific literature estimating the long-term retention rates is scarce. We estimate the factors affecting acceptance and retention of PPIUCD and explore the risk factors against PPIUCD Discontinuation at six months". MATERIAL AND METHOD: This prospective observational study was conducted between 2018 and 20 at a tertiary care institute in North India. PPIUCD was inserted following a detailed counseling session and consent. The women were followed up for six months. Bivariate analysis was done to depict the association between socio-demographic characteristics and acceptance. Logistic regression, cox regression, and Kaplan Meier analysis were applied to explore factors affecting acceptance and retention of PPIUCD. RESULTS: Of the 300 women counseled for PPIUCD, 60% accepted them. The majority of these women were between 25 and 30 years (40.6%), primigravida (61.7%), educated (86.1%), and from urban areas (61.7%). Retention rates at six months were about 65.6%, while 13.9% and 5.6% were either removed or expelled. Women declined PPIUCD due to refusal by spouses, partial knowledge, inclination towards other methods, non-willingness, religious beliefs, and fear of pain and heavy bleeding. Adjusted logistic regression depicted that higher education, housewife status, lower-middle and richest SES, Hinduism, and counseling in early pregnancy promoted acceptance of PPIUCD. The most common reasons for removal were AUB, infection, and family pressure (23.1%). Adjusted hazard ratio depicted religion other than Hinduism, counseling in late stages of pregnancy, and normal vaginal delivery were significant predictors for early removal or expulsion. While education, higher socio-economic status favoured retention. CONCLUSION: PPIUCD is a safe, highly effective, low-cost, long-acting, and feasible method of contraception. Skill enhancement of healthcare personnel for insertion techniques, adequate antenatal counseling, and advocacy of PPIUCD can help increase the acceptance of PPIUCD.

An update on SARS-CoV-2 immunization and future directions.

Millions of people have died as a result of SARS-CoV-2, which was first discovered in China and has since spread globally. Patients with SARS-CoV-2 infection may show a range of symptoms, including fever, coughing, and shortness of breath, or they may show no symptoms at all. To treat COVID-19 symptoms and avoid serious infections, many medications and vaccinations have been employed. However, to entirely eradicate COVID-19 from the world, next-generation vaccine research is required because of the devastating consequences it is having for humanity and every nation's economy. Scientists are working hard to eradicate this dangerous virus across the world. SARS-CoV-2 has also undergone significant mutation, leading to distinct viral types such as the alpha, beta, gamma, delta, and omicron variants. This has sparked discussion about the effectiveness of current vaccines for the newly formed variants. A proper comparison of these vaccinations is required to compare their efficacy as the number of people immunized against SARS-CoV-2 globally increases. Population-level statistics evaluating the capacity of these vaccines to reduce infection are therefore being developed. In this paper, we analyze the many vaccines on the market in terms of their production process, price, dosage needed, and efficacy. This article also discusses the challenges of achieving herd immunity, the likelihood of reinfection, and the importance of convalescent plasma therapy in reducing infection.

Pseudogout of the lumbar spine.

Calcium pyrophosphate deposition involves deposition of calcium pyrophosphate dihydrate crystals in various joints throughout the body. The term "pseudogout" refers to an acute attack of calcium pyrophosphate crystal-induced arthritis. Though clinical presentation and joint involvement vary, involvement of the lumbar spine is rare. We present the case of a 61-year-old male who presented with 3 days of worsening lower back pain. He had elevated inflammatory markers, leukocytosis, and spinal tenderness on exam. Magnetic resonance imaging of the lumbar spine showed likely L4-L5 osteomyelitis; however, biopsy of the disk space revealed extensive calcium pyrophosphate crystal deposition. The patient was treated with prednisone taper with alleviation of symptoms. Though pseudogout of the spine is rare, our report supports literature urging clinicians to consider pseudogout when assessing elderly patients with back pain for prompt and appropriate treatment.

Exosome-Functionalized, Drug-Laden Bone Substitute along with an Antioxidant Herbal Membrane for Bone and Periosteum Regeneration in Bone Sarcoma.

Developing advanced methods for effective bone reconstructive strategies in case of critical bone defects caused by tumor resection, trauma, and other implant-related complications remains a challenging problem in orthopedics. In the clinical management of bone diseases, there is a paradigm shift in using local drugs at the injury site; however, the dead space created during the surgical debridement of necrotic bone and soft tissues (periosteum and underlying muscle) leads to ineffective bone formation, thereby leading to secondary complications, and thus calls for better regenerative approaches. In this study, we have utilized an exosome-functionalized doxorubicin-loaded biodegradable nanocement (NC)-based carrier along with a Cissus quadrangularis (CQ) extract-laden antioxidant herbal membrane for simultaneously managing the periosteum as well as bone formation in the tumor resection model of osteosarcoma. We initially evaluated the efficacy of scaffolds for in vitro mineralization and bone formation. To examine the in vivo effectiveness, we developed a human osteosarcoma cell line (Saos-2)-induced tumor xenograft model with a critical-sized bone defect. The findings revealed that doxorubicin released from NC was successful in killing the tumor cells and was present even after 30 days of implantation. Additionally, the incorporation of exosomes aided the bone formation, resulting in around a 2.6-fold increase in the bone volume compared to the empty group as evaluated by micro-CT. The herbal membrane assisted in the development of periosteum and mineralizing bone callous as validated through histological and immunofluorescence analysis. Thus, our findings describe a one-step biomaterial-based cell-free approach to regenerate bone in osteosarcoma and prevent further fracture due to the complete development of periosteum and lost bone.

Universal architecture of corneal segmental tomography biomarkers for artificial intelligence-driven diagnosis of early keratoconus.

AIMS: To develop a comprehensive three-dimensional analyses of segmental tomography (placido and optical coherence tomography) using artificial intelligence (AI). METHODS: Preoperative imaging data (MS-39, CSO, Italy) of refractive surgery patients with stable outcomes and diagnosed with asymmetric or bilateral keratoconus (KC) were used. The curvature, wavefront aberrations and thickness distributions were analysed with Zernike polynomials (ZP) and a random forest (RF) AI model. For training and cross-validation, there were groups of healthy (n=527), very asymmetric ectasia (VAE; n=144) and KC (n=454). The VAE eyes were the fellow eyes of KC patients but no further manual segregation of these eyes into subclinical or forme-fruste was performed. RESULTS: The AI achieved an excellent area under the curve (0.994), accuracy (95.6%), recall (98.5%) and precision (92.7%) for the healthy eyes. For the KC eyes, the same were 0.997, 99.1%, 98.7% and 99.1%, respectively. For the VAE eyes, the same were 0.976, 95.5%, 71.5% and 91.2%, respectively. Interestingly, the AI reclassified 36 (subclinical) of the VAE eyes as healthy though these eyes were distinct from healthy eyes. Most of the remaining VAE (n=104; forme fruste) eyes retained their classification, and were distinct from both KC and healthy eyes. Further, the posterior surface features were not among the highest ranked variables by the AI model. CONCLUSIONS: A universal architecture of combining segmental tomography with ZP and AI was developed. It achieved an excellent classification of healthy and KC eyes. The AI efficiently classified the VAE eyes as 'subclinical' and 'forme-fruste'.

Biochemical Changes in Two Barley Genotypes Inoculated With a Beneficial Fungus Trichoderma harzianum Rifai T-22 Grown in Saline Soil.

One of the most important environmental factors impacting crop plant productivity is soil salinity. Fungal endophytes have been characterised as biocontrol agents that help in plant productivity and induce resistance responses to several abiotic stresses, including salinity. In the salt-tolerant cereal crop barley (Hordeum vulgare L.), there is limited information about the metabolites and lipids that change in response to inoculation with fungal endophytes in saline conditions. In this study, gas chromatography coupled to mass spectrometry (GC-MS) and LC-electrospray ionisation (ESI)-quadrupole-quadrupole time of flight (QqTOF)-MS were used to determine the metabolite and lipid changes in two fungal inoculated barley genotypes with differing tolerance levels to saline conditions. The more salt-tolerant cultivar was Vlamingh and less salt tolerant was Gairdner. Trichoderma harzianum strain T-22 was used to treat these plants grown in soil under control and saline (200 mM NaCl) conditions. For both genotypes, fungus-colonised plants exposed to NaCl had greater root and shoot biomass, and better chlorophyll content than non-colonised plants, with colonised-Vlamingh performing better than uninoculated control plants. The metabolome dataset using GC-MS consisted of a total of 93 metabolites of which 74 were identified in roots of both barley genotypes as organic acids, sugars, sugar acids, sugar alcohols, amino acids, amines, and a small number of fatty acids. LC-QqTOF-MS analysis resulted in the detection of 186 lipid molecular species, classified into three major lipid classes-glycerophospholipids, glycerolipids, and sphingolipids, from roots of both genotypes. In Cultivar Vlamingh both metabolites and lipids increased with fungus and salt treatment while in Gairdner they decreased. The results from this study suggest that the metabolic pathways by which the fungus imparts salt tolerance is different for the different genotypes.

Impact of tear optics on the repeatability of Pentacam AXL wave and iTrace in measuring anterior segment parameters and aberrations.

Purpose: To assess impact of tear optics on repeatability of a Scheimpflug device with a Hartmann Shack aberrometer and a ray tracing aberrometer. Methods: One hundred healthy and 100 postrefractive surgery eyes underwent dry eye evaluation including Schirmer's test and tear film break-up time (TBUT). They underwent optical quality analyzer (OQAS, Visio metrics S.L, Terrassa, Spain) to assess objective scatter index (OSI), three scans each on Pentacam AXL wave (OCULUS Optikgerate Gmbh, Wetzlar, Germany), iTrace (Tracey™ Technologies, Texas, USA) for flat, steep keratometry, thinnest corneal thickness, root mean square higher-order aberrations (RMS HOA), RMS lower-order aberrations (LOA), spherical aberrations, RMS COMA. Repeatability of Pentacam AXL wave and iTrace in healthy and postrefractive eyes (OSI >1 vs OSI <1) was studied using within-subject standard deviation (Sw) test-retest repeatability (TRT), coefficient of variation (COV). Results: OSI showed an inverse association with TBUT (P < 0.001). All measurements with Pentacam AXL wave with OSI < 1 had excellent repeatability, intraclass correlation coefficient (ICC) ranging from 0.88 for HOA, to 0.92 for LOA. The Sw, TRT, and COV of all aberration measurements were significantly lower (better) than those of iTrace. In eyes with OSI ≥1, the repeatability with Pentacam AXL wave dropped with ICC ranging from 0.77 for HOA, to 0.84 for LOA with lower Sw, TRT, and COV of all aberration measurements as compared to iTrace. Maximum variation was seen with HOA and minimum with LOA. Conclusion: Tear optics affected repeatability of Pentacam wave and iTrace. Pentacam wave had better repeatability in eyes with a poor tear film as compared to iTrace. Thus, the tear film can impact repeatability of an instrument and it is important to assess the tear film prior to imaging patients, which can change the way we interpret and image these patients.

Metabolomics as an emerging tool to study plant-microbe interactions.

In natural environments, interaction between plant roots and microorganisms are common. These interactions between microbial species and plants inhabited by them are being studied using various techniques. Metabolomics research based on mass spectrometric techniques is one of the crucial approaches that underpins system biology and relies on precision instrument analysis. In the last decade, this emerging field has received extensive attention. It provides a qualitative and quantitative approach for determining the mechanisms of symbiosis of bacteria and fungi with plants and also helps to elucidate the tolerance mechanisms of host plants against various abiotic stresses. However, this -omics application and its tools in plant-microbe interaction studies is still underutilized compared with genomic and transcriptomic methods. Therefore, it is crucial to bring this field forward to bear on the study of plant resistance and susceptibility. This review describes the current status of methods and progress in metabolomics applications for plant-microbe interaction studies discussing current challenges and future prospects.

An Artificial Intelligence Chatbot for Young People's Sexual and Reproductive Health in India (SnehAI): Instrumental Case Study.

BACKGROUND: Leveraging artificial intelligence (AI)-driven apps for health education and promotion can help in the accomplishment of several United Nations sustainable development goals. SnehAI, developed by the Population Foundation of India, is the first Hinglish (Hindi + English) AI chatbot, deliberately designed for social and behavioral changes in India. It provides a private, nonjudgmental, and safe space to spur conversations about taboo topics (such as safe sex and family planning) and offers accurate, relatable, and trustworthy information and resources. OBJECTIVE: This study aims to use the Gibson theory of affordances to examine SnehAI and offer scholarly guidance on how AI chatbots can be used to educate adolescents and young adults, promote sexual and reproductive health, and advocate for the health entitlements of women and girls in India. METHODS: We adopted an instrumental case study approach that allowed us to explore SnehAI from the perspectives of technology design, program implementation, and user engagement. We also used a mix of qualitative insights and quantitative analytics data to triangulate our findings. RESULTS: SnehAI demonstrated strong evidence across fifteen functional affordances: accessibility, multimodality, nonlinearity, compellability, queriosity, editability, visibility, interactivity, customizability, trackability, scalability, glocalizability, inclusivity, connectivity, and actionability. SnehAI also effectively engaged its users, especially young men, with 8.2 million messages exchanged across a 5-month period. Almost half of the incoming user messages were texts of deeply personal questions and concerns about sexual and reproductive health, as well as allied topics. Overall, SnehAI successfully presented itself as a trusted friend and mentor; the curated content was both entertaining and educational, and the natural language processing system worked effectively to personalize the chatbot response and optimize user experience. CONCLUSIONS: SnehAI represents an innovative, engaging, and educational intervention that enables vulnerable and hard-to-reach population groups to talk and learn about sensitive and important issues. SnehAI is a powerful testimonial of the vital potential that lies in AI technologies for social good.

Clinical and Preclinical Single-Dose Pharmacokinetics of VIR-2218, an RNAi Therapeutic Targeting HBV Infection.

BACKGROUND AND OBJECTIVE: VIR-2218 is an investigational N-acetylgalactosamine-conjugated RNA interference therapeutic in development for chronic hepatitis B virus (HBV) infection. VIR-2218 was designed to silence HBV transcripts across all genotypes and uses Enhanced Stabilization Chemistry Plus (ESC+) technology. This study was designed to evaluate the single-dose pharmacokinetics of VIR-2218 in preclinical species and healthy volunteers. METHODS: Preclinically, a single subcutaneous dose of VIR-2218 (10 mg/kg) was administered to rats and nonhuman primates (NHPs), and the pharmacokinetics were assessed in plasma, urine, and liver using standard noncompartmental analysis (NCA) methods. Clinically, healthy volunteers were randomized (6:2 active:placebo) to receive a single subcutaneous dose of VIR-2218 (50-900 mg) or placebo. Pharmacokinetics were similarly assessed within human plasma and urine using NCA methods. RESULTS: In rats and NHPs, VIR-2218 was stable in plasma and was converted to AS(N-1)3'VIR-2218, the most prominent circulating metabolite, at < 10% plasma exposure compared with parent. VIR-2218 rapidly distributed to the liver, reaching peak liver concentrations within 7 and 24 h in rats and NHPs, respectively. In humans, VIR-2218 was rapidly absorbed, with a median time to peak plasma concentration (tmax) of 4-7 h, and had a short median plasma half-life of 2-5 h. Plasma exposures for area under the plasma concentration-time curve up to 12 h (AUC0-12) and mean maximum concentrations (Cmax) increased in a slightly greater-than-dose-proportional manner across the dose range studied. Interindividual pharmacokinetic variability was low to moderate, with a percent coefficient of variation of < 32% for AUC and < 43% for Cmax. A portion of VIR-2218 was converted to an active metabolite, AS(N-1)3'VIR-2218, with a median tmax of 6-10 h, both of which declined below the lower limit of quantification in plasma within 48 h. The pharmacokinetic profile of AS(N-1)3'VIR-2218 was similar to that of VIR-2218, with plasma AUC0-12 and Cmax values ≤ 12% of VIR-2218. VIR-2218 and AS(N-1)3'VIR-2218 were detectable in urine through the last measured time point, with approximately 17-48% of the administered dose recovered in urine as unchanged VIR-2218 over 0-24 h postdose. Based on pharmacokinetics in preclinical species, VIR-2218 localizes to the liver and likely exhibits prolonged hepatic exposure. Overall, no severe or serious adverse events or discontinuations due to adverse events were observed within the dose range evaluated for VIR-2218 in healthy volunteers (Vir Biotechnology, Inc., unpublished data). CONCLUSIONS: VIR-2218 showed favorable pharmacokinetics in healthy volunteers supportive of subcutaneous dosing and continued development in patients with chronic HBV infection. CLINICAL TRIAL REGISTRATION NO: NCT03672188, September 14, 2018.

Keratoconus patients exhibit a distinct ocular surface immune cell and inflammatory profile.

Inflammatory factors have been considered to contribute to keratoconus (KC) pathogenesis. This study aims to determine the immune cells subsets and soluble inflammatory factor profile on the ocular surface of KC patients. 32 KC subjects (51 eyes) across different grades of severity and 15 healthy controls (23 eyes) were included in the study. Keratometry and pachymetry measurements were recorded. Ocular surface immune cells (collected by ocular surface wash) immunophenotyped using flow cytometry include leukocytes, neutrophils, macrophages, natural killer (NK) cells, pan-T cells, gamma delta T (γδT) cells and NKT cells. Tear fluid collected using Schirmer's strip was used to measure 50 soluble factors by multiplex ELISA. Proportions of activated neutrophils, NK cells and γδT cells were significantly increased in KC patients. Significantly higher levels of tear fluid IL-1ß, IL-6, LIF, IL-17A, TNFα, IFNα/ß/γ, EPO, TGFß1, PDGF-BB, sVCAM, sL-selectin, granzyme-B, perforin, MMP2, sFasL and IgE, along with significantly lower levels of IL-1α and IL-9 were observed in KC patients. Alterations observed in few of the immuno-inflammatory parameters correlated with grades of disease, allergy, eye rubbing and keratometry or pachymetry measurements. The observation implies a distinct immuno-inflammatory component in KC pathogenesis and its potential as an additional therapeutic target in KC management.

A Clinical Study to Evaluate the Association Between Metabolic Syndrome and Sensorineural Hearing Loss.

Metabolic syndrome is considered to be a triggering factor for deterioration of health related quality of life. In present study we assessed hearing loss consequent to metabolic syndrome. A total of 100 patients diagnosed for metabolic syndrome (IDF criteria) were included in the study. All the patients underwent pure tone audiometry and impedance audiometry. All the patients underwent anthropometric measurements, lipid profile, blood sugar and blood pressure assessments. Data was analyzed using SPSS 21.0 software. A total of 62% patients had sensorineural hearing loss. Maximum (35%) had mild hearing loss, followed by moderate hearing loss (23%). Only 4 (4%) cases had severe hearing loss. Older age, wider waist circumference, higher fasting blood glucose levels and lower blood pressure were found to be significantly associated with sensorineural hearing loss and its severity on univariate analysis. However, on multivariate assessment only age and waist circumference showed a significant association with hearing loss.

Inoculation of barley with Trichoderma harzianum T-22 modifies lipids and metabolites to improve salt tolerance.

Soil salinity has a serious impact on plant growth and agricultural yield. Inoculation of crop plants with fungal endophytes is a cost-effective way to improve salt tolerance. We used metabolomics to study how Trichoderma harzianum T-22 alleviates NaCl-induced stress in two barley (Hordeum vulgare L.) cultivars, Gairdner and Vlamingh, with contrasting salinity tolerance. GC-MS was used to analyse polar metabolites and LC-MS to analyse lipids in roots during the early stages of interaction with Trichoderma. Inoculation reversed the severe effects of salt on root length in sensitive cv. Gairdner and, to a lesser extent, improved root growth in more tolerance cv. Vlamingh. Biochemical changes showed a similar pattern in inoculated roots after salt treatment. Sugars increased in both cultivars, with ribulose, ribose, and rhamnose specifically increased by inoculation. Salt stress caused large changes in lipids in roots but inoculation with fungus greatly reduced the extent of these changes. Many of the metabolic changes in inoculated cv. Gairdner after salt treatment mirror the response of uninoculated cv. Vlamingh, but there are some metabolites that changed in both cultivars only after fungal inoculation. Further study is required to determine how these metabolic changes are induced by fungal inoculation.