The Role of Seminal Oxidative Stress in Recurrent Pregnancy Loss.

Recurrent pregnancy loss is a distressing condition affecting 1-2% of couples. Traditionally investigations have focused on the female, however more recently researchers have started to explore the potential contribution of the male partner. Seminal reactive oxygen species have a physiological function in male reproduction but in excess are suspected to generate structural and functional damage to the sperm. Evidence is mounting to support an association between elevated seminal reaction oxygen species and recurrent pregnancy loss. Studies suggest that the rates of sperm DNA damage are higher in the male partners of women affected by recurrent pregnancy loss compared with unaffected men. However, the available pool of data is conflicting, and interpretation is limited by the recent change in nomenclature and the heterogeneity of study methodologies. Furthermore, investigation into the effects of oxidative stress on the epigenome show promise. The value of antioxidant therapy in the management of recurrent pregnancy loss currently remains unclear.

Screening of phytochemicals as potential anti-breast cancer agents targeting HER2: an in-silico approach.

Breast cancer is the most common cancer among women around the world. Human Epidermal growth factor Receptor-2 (HER2) is a membrane tyrosine kinase overexpressed in 30% of human breast cancers; thus, it serves as an important drug target. Currently available HER2 inhibitor lapatinib targets the ATP binding site of the cytoplasmic kinase domain, blocking autophosphorylation and activation of HER-2. However, it causes side effects like diarrhea, nausea, rash and possible liver toxicity. As phytochemicals have fewer side effects and are relatively affordable, they offer an effective alternative. Hence, we aimed to identify potential phytochemicals that could act as HER2 inhibitors employing computational methods such as molecular docking, molecular dynamic simulation, and ADMET prediction. Out of 1500 phytochemicals docked to the ATP binding site of the HER2 kinase domain, luxenchalcone, rhinacanthin Q, subtrifloralacton D, and 7,7″-dimethyllanaraflavone exhibited higher binding affinity than the reference inhibitor and satisfied the Lipinski's rule of five. Analysis of molecular dynamics simulation trajectory showed that Rhinacanthin Q, subtrifloralacton D, and 7,7″-dimethyllanaraflavone formed a stable and compact complex without vast conformational fluctuations. MM/PBSA binding free energy analysis revealed that Rhinacanthin Q, subtrifloralacton D, and 7,7″-dimethyllanaraflavone have high binding affinity to HER2. Therefore, Rhinacanthin Q, subtrifloralacton D, and 7,7″-dimethyllanaraflavone could be potential bioactive molecules to act as inhibitor of HER2 protein. Eventually, experimental studies are needed to evaluate the potentials of these phytochemicals further. The development of drug for HER2 positive breast cancer could be accelerated with the findings of our research. Communicated by Ramaswamy H. Sarma.

Design of Smart Nanodiamonds: Introducing pH Sensitivity to Improve Nucleic Acid Carrier Efficiency of Diamoplexes.

The mechanism of cellular uptake and intracellular fate of nanodiamond/nucleic acid complexes (diamoplexes) are major determinants of its performance as a gene carrier. Our group designed lysine-nanodiamonds (K-NDs) as vectors for nucleic acid delivery. In this work, we modified the surface of K-NDs with histidine to overcome endo-lysosomal entrapment diamoplexes, the major rate limiting step in gene transfer. Histidine is conjugated onto the NDs in two configurations: lysyl-histidine-NDs (HK-NDs) where histidine is loaded on 100% of the lysine moieties and lysine/lysyl-histidine-NDs (H50K50-NDs) where histidine is loaded on 50% of the lysine moieties. Both HK-NDs and H50K50-NDs maintained the optimum size distribution (i.e., <200 nm) and a cationic surface (zeta potential > 20 mV), similar to K-NDs. HK-NDs binds plasmid deoxyribonucleic acid (pDNA) and small interfering ribonucleic acid (siRNA) forming diamoplexes at mass ratios of 10:1 and 60:1, respectively. H50K50-NDs significantly improved nucleic acid binding, forming diamoplexes at a 2:1 mass ratio with pDNA and a 30:1 mass ratio with siRNA, which are at values similar to the K-NDs. The amount of histidine on the surface also impacted the interactions with mammalian cells. The HK-NDs reduced the cell viability by 30% at therapeutic concentrations, while H50K50-NDs maintained more than 90% cell viability, even at the highest concentrations. H50K50-NDs also showed highest cellular uptake within 24 h, followed by K-NDs and HK-NDs. Most functionalized NDs show cellular exit after 5 days, leaving less than 10% of cells with internalized diamonds. The addition of histidine to the ND resulted in higher transfection of anti-green fluorescent protein siRNA (anti-GFP siRNA) with the fraction of GFP knockdown being 0.8 vs. 0.6 for K-NDs at a mass ratio of 50:1. H50K50-NDs further improved transfection by achieving a similar fraction of GFP knockdown (0.8) at a lower mass ratio of 30:1. Overall, this study provides evidence that the addition of histidine, a pH-modulating entity in the functionalization design at an optimized ratio, renders high efficiency to the diamoplexes. Further studies will elucidate the uptake mechanism and intracellular fate to build the relationship between physicochemical characteristics and biological efficacy and create a platform for solid-core nanoparticle-based gene delivery.

Chitosan Nanoparticles at the Biological Interface: Implications for Drug Delivery.

The unique properties of chitosan make it a useful choice for various nanoparticulate drug delivery applications. Although chitosan is biocompatible and enables cellular uptake, its interactions at cellular and systemic levels need to be studied in more depth. This review focuses on the various physical and chemical properties of chitosan that affect its performance in biological systems. We aim to analyze recent research studying interactions of chitosan nanoparticles (NPs) upon their cellular uptake and their journey through the various compartments of the cell. The positive charge of chitosan enables it to efficiently attach to cells, increasing the probability of cellular uptake. Chitosan NPs are taken up by cells via different pathways and escape endosomal degradation due to the proton sponge effect. Furthermore, we have reviewed the interaction of chitosan NPs upon in vivo administration. Chitosan NPs are immediately surrounded by a serum protein corona in systemic circulation upon intravenous administration, and their biodistribution is mainly to the liver and spleen indicating RES uptake. However, the evasion of RES system as well as the targeting ability and bioavailability of chitosan NPs can be improved by utilizing specific routes of administration and covalent modifications of surface properties. Ongoing clinical trials of chitosan formulations for therapeutic applications are paving the way for the introduction of chitosan into the pharmaceutical market and for their toxicological evaluation. Chitosan provides specific biophysical properties for effective and tunable cellular uptake and systemic delivery for a wide range of applications.

Miscarriage matters: the epidemiological, physical, psychological, and economic costs of early pregnancy loss.

Miscarriage is generally defined as the loss of a pregnancy before viability. An estimated 23 million miscarriages occur every year worldwide, translating to 44 pregnancy losses each minute. The pooled risk of miscarriage is 15·3% (95% CI 12·5-18·7%) of all recognised pregnancies. The population prevalence of women who have had one miscarriage is 10·8% (10·3-11·4%), two miscarriages is 1·9% (1·8-2·1%), and three or more miscarriages is 0·7% (0·5-0·8%). Risk factors for miscarriage include very young or older female age (younger than 20 years and older than 35 years), older male age (older than 40 years), very low or very high body-mass index, Black ethnicity, previous miscarriages, smoking, alcohol, stress, working night shifts, air pollution, and exposure to pesticides. The consequences of miscarriage are both physical, such as bleeding or infection, and psychological. Psychological consequences include increases in the risk of anxiety, depression, post-traumatic stress disorder, and suicide. Miscarriage, and especially recurrent miscarriage, is also a sentinel risk marker for obstetric complications, including preterm birth, fetal growth restriction, placental abruption, and stillbirth in future pregnancies, and a predictor of longer-term health problems, such as cardiovascular disease and venous thromboembolism. The costs of miscarriage affect individuals, health-care systems, and society. The short-term national economic cost of miscarriage is estimated to be £471 million per year in the UK. As recurrent miscarriage is a sentinel marker for various obstetric risks in future pregnancies, women should receive care in preconception and obstetric clinics specialising in patients at high risk. As psychological morbidity is common after pregnancy loss, effective screening instruments and treatment options for mental health consequences of miscarriage need to be available. We recommend that miscarriage data are gathered and reported to facilitate comparison of rates among countries, to accelerate research, and to improve patient care and policy development.

Recurrent miscarriage: evidence to accelerate action.

Women who have had repeated miscarriages often have uncertainties about the cause, the likelihood of recurrence, the investigations they need, and the treatments that might help. Health-care policy makers and providers have uncertainties about the optimal ways to organise and provide care. For this Series paper, we have developed recommendations for practice from literature reviews, appraisal of guidelines, and a UK-wide consensus conference that was held in December, 2019. Caregivers should individualise care according to the clinical needs and preferences of women and their partners. We define a minimum set of investigations and treatments to be offered to couples who have had recurrent miscarriages, and urge health-care policy makers and providers to make them universally available. The essential investigations include measurements of lupus anticoagulant, anticardiolipin antibodies, thyroid function, and a transvaginal pelvic ultrasound scan. The key treatments to consider are first trimester progesterone administration, levothyroxine in women with subclinical hypothyroidism, and the combination of aspirin and heparin in women with antiphospholipid antibodies. Appropriate screening and care for mental health issues and future obstetric risks, particularly preterm birth, fetal growth restriction, and stillbirth, will need to be incorporated into the care pathway for couples with a history of recurrent miscarriage. We suggest health-care services structure care using a graded model in which women are offered online health-care advice and support, care in a nurse or midwifery-led clinic, and care in a medical consultant-led clinic, according to clinical needs.

The Prevalence of Thyroid Dysfunction and Autoimmunity in Women With History of Miscarriage or Subfertility.

OBJECTIVE: To describe the prevalence of and factors associated with different thyroid dysfunction phenotypes in women who are asymptomatic preconception. DESIGN: Observational cohort study. SETTING: A total of 49 hospitals across the United Kingdom between 2011 and 2016. PARTICIPANTS: Women aged 16 to 41years with history of miscarriage or subfertility trying for a pregnancy. METHODS: Prevalences and 95% confidence intervals (CIs) were estimated using the binomial exact method. Multivariate logistic regression analyses were conducted to identify risk factors for thyroid disease. INTERVENTION: None. MAIN OUTCOME MEASURE: Rates of thyroid dysfunction. RESULTS: Thyroid function and thyroid peroxidase antibody (TPOAb) data were available for 19213 and 19237 women, respectively. The prevalence of abnormal thyroid function was 4.8% (95% CI, 4.5-5.1); euthyroidism was defined as levels of thyroid-stimulating hormone (TSH) of 0.44 to 4.50 mIU/L and free thyroxine (fT4) of 10 to 21 pmol/L. Overt hypothyroidism (TSH > 4.50 mIU/L, fT4 < 10 pmol/L) was present in 0.2% of women (95% CI, 0.1-0.3) and overt hyperthyroidism (TSH < 0.44 mIU/L, fT4 > 21 pmol/L) was present in 0.3% (95% CI, 0.2-0.3). The prevalence of subclinical hypothyroidism (SCH) using an upper TSH concentration of 4.50 mIU/L was 2.4% (95% CI, 2.1-2.6). Lowering the upper TSH to 2.50 mIU/L resulted in higher rates of SCH, 19.9% (95% CI, 19.3-20.5). Multiple regression analyses showed increased odds of SCH (TSH > 4.50 mIU/L) with body mass index (BMI) ≥ 35.0 kg/m2 (adjusted odds ratio [aOR] 1.71; 95% CI, 1.13-2.57; P = 0.01) and Asian ethnicity (aOR 1.76; 95% CI, 1.31-2.37; P < 0.001), and increased odds of SCH (TSH ≥ 2.50 mIU/L) with subfertility (aOR 1.16; 95% CI, 1.04-1.29; P = 0.008). TPOAb positivity was prevalent in 9.5% of women (95% CI, 9.1-9.9). CONCLUSIONS: The prevalence of undiagnosed overt thyroid disease is low. SCH and TPOAb are common, particularly in women with higher BMI or of Asian ethnicity. A TSH cutoff of 2.50 mIU/L to define SCH results in a significant proportion of women potentially requiring levothyroxine treatment.

Micronized vaginal progesterone to prevent miscarriage: a critical evaluation of randomized evidence.

Progesterone is essential for the maintenance of pregnancy. Several small trials have suggested that progesterone supplementation may reduce the risk of miscarriage in women with recurrent or threatened miscarriage. Cochrane Reviews summarized the evidence and found that the trials were small with substantial methodologic weaknesses. Since then, the effects of first-trimester use of vaginal micronized progesterone have been evaluated in 2 large, high-quality, multicenter placebo-controlled trials, one targeting women with unexplained recurrent miscarriages (the PROMISE [PROgesterone in recurrent MIScarriagE] trial) and the other targeting women with early pregnancy bleeding (the PRISM [PRogesterone In Spontaneous Miscarriage] trial). The PROMISE trial studied 836 women from 45 hospitals in the United Kingdom and the Netherlands and found a 3% greater live birth rate with progesterone but with substantial statistical uncertainty. The PRISM trial studied 4153 women from 48 hospitals in the United Kingdom and found a 3% greater live birth rate with progesterone, but with a P value of .08. A key finding, first observed in the PROMISE trial, and then replicated in the PRISM trial, was that treatment with vaginal micronized progesterone 400 mg twice daily was associated with increasing live birth rates according to the number of previous miscarriages. Prespecified PRISM trial subgroup analysis in women with the dual risk factors of previous miscarriage(s) and current pregnancy bleeding fulfilled all 11 conditions for credible subgroup analysis. For the subgroup of women with a history of 1 or more miscarriage(s) and current pregnancy bleeding, the live birth rate was 75% (689/914) with progesterone vs 70% (619/886) with placebo (rate difference 5%; risk ratio, 1.09, 95% confidence interval, 1.03-1.15; P=.003). The benefit was greater for the subgroup of women with 3 or more previous miscarriages and current pregnancy bleeding; live birth rate was 72% (98/137) with progesterone vs 57% (85/148) with placebo (rate difference 15%; risk ratio, 1.28, 95% confidence interval, 1.08-1.51; P=.004). No short-term safety concerns were identified from the PROMISE and PRISM trials. Therefore, women with a history of miscarriage who present with bleeding in early pregnancy may benefit from the use of vaginal micronized progesterone 400 mg twice daily. Women and their care providers should use the findings for shared decision-making.

FSH Requirements for Follicle Growth During Controlled Ovarian Stimulation.

Introduction: Ovarian follicle growth is a key step in the success of assisted reproductive treatment, but limited data exists to directly relate follicle growth to recombinant FSH (rFSH) dose. In this study, we aim to evaluate FSH requirements for follicular growth during controlled ovarian stimulation. Method: Single center retrospective cohort study of 1,034 IVF cycles conducted between January 2012-January 2016 at Hammersmith Hospital IVF unit, London, UK. Median follicle size after 5 days of stimulation with rFSH and the proportion of antral follicles recruited were analyzed in women treated with rFSH alone to induce follicular growth during IVF treatment. Results: Starting rFSH dose adjusted for body weight (iU/kg) predicted serum FSH level after 5 days of rFSH (r 2 = 0.352, p < 0.0001), median follicle size after 5 days of rFSH, and the proportion of antral follicles recruited by the end of stimulation. Day 5 median follicle size predicted median follicle size on subsequent ultrasound scans (r 2 = 0.58-0.62; p < 0.0001), and hence time to oocyte maturation trigger (r 2 = 0.22, P < 0.0001). Insufficient rFSH starting dose that required >5% dose-increase was associated with increased variability in follicle size on the day of oocyte maturation trigger, and negatively impacted the number of mature oocytes retrieved. Conclusion: Weight-adjusted rFSH dose correlates with follicular growth during ovarian stimulation. Early recruitment of follicles using a sufficient dose of rFSH from the start of stimulation was associated with reduced variability in follicle size at time of oocyte maturation trigger and an increased number of mature oocytes retrieved.

Polymeric Nanoparticles in Gene Therapy: New Avenues of Design and Optimization for Delivery Applications.

The field of polymeric nanoparticles is quickly expanding and playing a pivotal role in a wide spectrum of areas ranging from electronics, photonics, conducting materials, and sensors to medicine, pollution control, and environmental technology. Among the applications of polymers in medicine, gene therapy has emerged as one of the most advanced, with the capability to tackle disorders from the modern era. However, there are several barriers associated with the delivery of genes in the living system that need to be mitigated by polymer engineering. One of the most crucial challenges is the effectiveness of the delivery vehicle or vector. In last few decades, non-viral delivery systems have gained attention because of their low toxicity, potential for targeted delivery, long-term stability, lack of immunogenicity, and relatively low production cost. In 1987, Felgner et al. used the cationic lipid based non-viral gene delivery system for the very first time. This breakthrough opened the opportunity for other non-viral vectors, such as polymers. Cationic polymers have emerged as promising candidates for non-viral gene delivery systems because of their facile synthesis and flexible properties. These polymers can be conjugated with genetic material via electrostatic attraction at physiological pH, thereby facilitating gene delivery. Many factors influence the gene transfection efficiency of cationic polymers, including their structure, molecular weight, and surface charge. Outstanding representatives of polymers that have emerged over the last decade to be used in gene therapy are synthetic polymers such as poly(l-lysine), poly(l-ornithine), linear and branched polyethyleneimine, diethylaminoethyl-dextran, poly(amidoamine) dendrimers, and poly(dimethylaminoethyl methacrylate). Natural polymers, such as chitosan, dextran, gelatin, pullulan, and synthetic analogs, with sophisticated features like guanidinylated bio-reducible polymers were also explored. This review outlines the introduction of polymers in medicine, discusses the methods of polymer synthesis, addressing top down and bottom up techniques. Evaluation of functionalization strategies for therapeutic and formulation stability are also highlighted. The overview of the properties, challenges, and functionalization approaches and, finally, the applications of the polymeric delivery systems in gene therapy marks this review as a unique one-stop summary of developments in this field.

Levothyroxine in Women with Thyroid Peroxidase Antibodies before Conception.

BACKGROUND: Thyroid peroxidase antibodies are associated with an increased risk of miscarriage and preterm birth, even when thyroid function is normal. Small trials indicate that the use of levothyroxine could reduce the incidence of such adverse outcomes. METHODS: We conducted a double-blind, placebo-controlled trial to investigate whether levothyroxine treatment would increase live-birth rates among euthyroid women who had thyroid peroxidase antibodies and a history of miscarriage or infertility. A total of 19,585 women from 49 hospitals in the United Kingdom underwent testing for thyroid peroxidase antibodies and thyroid function. We randomly assigned 952 women to receive either 50 µg once daily of levothyroxine (476 women) or placebo (476 women) before conception through the end of pregnancy. The primary outcome was live birth after at least 34 weeks of gestation. RESULTS: The follow-up rate for the primary outcome was 98.7% (940 of 952 women). A total of 266 of 470 women in the levothyroxine group (56.6%) and 274 of 470 women in the placebo group (58.3%) became pregnant. The live-birth rate was 37.4% (176 of 470 women) in the levothyroxine group and 37.9% (178 of 470 women) in the placebo group (relative risk, 0.97; 95% confidence interval [CI], 0.83 to 1.14, P = 0.74; absolute difference, -0.4 percentage points; 95% CI, -6.6 to 5.8). There were no significant between-group differences in other pregnancy outcomes, including pregnancy loss or preterm birth, or in neonatal outcomes. Serious adverse events occurred in 5.9% of women in the levothyroxine group and 3.8% in the placebo group (P = 0.14). CONCLUSIONS: The use of levothyroxine in euthyroid women with thyroid peroxidase antibodies did not result in a higher rate of live births than placebo. (Funded by the United Kingdom National Institute for Health Research; TABLET Current Controlled Trials number, ISRCTN15948785.).

18-Fluoride labeled sodium fluoride positron emission tomography with computer tomography: the impact of pretreatment staging in intermediate- and high-risk prostate cancer.

BACKGROUND: 18-Fluoride labeled sodium fluoride (Na-18-F) positron emission tomography with computer tomography (PET/CT) has a better sensitivity and specificity than whole body bone scan (WBBS) in detecting osseous metastatic prostate cancer. We performed a pilot study of 20 men to examine what level of impact Na-18-F PET/CT has on management plans when used for staging newly diagnosed prostate cancer. MATERIALS AND METHODS: Twenty men were prospectively enrolled into the study in South Australia. Men were eligible if they had newly diagnosed, untreated, and biopsy-confirmed intermediate- or high-risk prostate cancer (D'Amico classification). WBBS and Na-18-F PET/CT scans were performed within 1 week of each other. Following review of the WBBS, treatment type and intent was documented by the treating urologist. The Na-18-F PET/CT scan was then reviewed. The impact of the Na-18-F PET/CT was measured on whether treatment modality or intent was subsequently altered: high impact = treatment intent or modality was changed; medium impact = treatment modality was modified; low impact = no change in treatment. RESULTS: In 18 men (90%), the WBBS and Na-18-F PET/CT were negative for osseous metastases. In one man (5%), the WBBS demonstrated widespread osseous metastases which were similarly demonstrated on the Na-18-F PET/CT. One man (5%) had a normal WBBS; however, the Na-18-F PET/CT demonstrated widespread osseous metastases. Subsequently, in 19 men (95%), the results of the two scans were congruent and the addition of the Na-18-F PET/CT scan demonstrated a low impact on management. In one man (5%), the addition of the Na-18-F PET/CT had a high impact as treatment type and intent was altered. CONCLUSIONS: Our pilot study is the first of its kind in Australia, and our findings suggest that Na-18-F PET/CT is a safe and feasible modality for staging prostate cancer. However, its true impact on prostate cancer management warrants further investigation.

SSH Analysis of Endosperm Transcripts and Characterization of Heat Stress Regulated Expressed Sequence Tags in Bread Wheat.

Heat stress is one of the major problems in agriculturally important cereal crops, especially wheat. Here, we have constructed a subtracted cDNA library from the endosperm of HS-treated (42°C for 2 h) wheat cv. HD2985 by suppression subtractive hybridization (SSH). We identified ~550 recombinant clones ranging from 200 to 500 bp with an average size of 300 bp. Sanger's sequencing was performed with 205 positive clones to generate the differentially expressed sequence tags (ESTs). Most of the ESTs were observed to be localized on the long arm of chromosome 2A and associated with heat stress tolerance and metabolic pathways. Identified ESTs were BLAST search using Ensemble, TriFLD, and TIGR databases and the predicted CDS were translated and aligned with the protein sequences available in pfam and InterProScan 5 databases to predict the differentially expressed proteins (DEPs). We observed eight different types of post-translational modifications (PTMs) in the DEPs corresponds to the cloned ESTs-147 sites with phosphorylation, 21 sites with sumoylation, 237 with palmitoylation, 96 sites with S-nitrosylation, 3066 calpain cleavage sites, and 103 tyrosine nitration sites, predicted to sense the heat stress and regulate the expression of stress genes. Twelve DEPs were observed to have transmembrane helixes (TMH) in their structure, predicted to play the role of sensors of HS. Quantitative Real-Time PCR of randomly selected ESTs showed very high relative expression of HSP17 under HS; up-regulation was observed more in wheat cv. HD2985 (thermotolerant), as compared to HD2329 (thermosusceptible) during grain-filling. The abundance of transcripts was further validated through northern blot analysis. The ESTs and their corresponding DEPs can be used as molecular marker for screening or targeted precision breeding program. PTMs identified in the DEPs can be used to elucidate the thermotolerance mechanism of wheat-a novel step toward the development of "climate-smart" wheat.

Exposed Dental Implant? Local Autograft A Saviour!

Implant exposure due to faulty placement, posses as the most common reason for implant failure. The implant placed too close to buccal or lingual cortex have lead to such failure on numerous occasions. Also, anatomic variations like the thin buccolingual width of alveolar ridge predispose exposure of the implant. 25-year-old female patient had undergone surgical placement of implants in mandibular anterior region 2 months back in the private dental clinic. The clinician noted Grade I mobility in one of the implants placed. The case was referred to the author. Thin overlying gingiva depicted an entire buccal aspect of the implant, which suggested more than 90 % loss of buccal cortex. According to literature and review of similar case reports, the only way suggested was to surgically remove the implant and wait for 12-24 months for the bone to heal for subsequent placement. Rather than the removal of implants as suggested, the author followed a naval approach of reinforcing buccal cortex using an autogenous cortical block from mandibular symphysis. The reinforcement surgery had certainly saved patients time, money and most importantly limits a crucial period of edentulism, which may be enforced on a patient in case the implant was removed.

Tissue Engineering: Step Ahead in Maxillofacial Reconstruction.

Within the precedent decade, a new field of "tissue engineering" or "tissue regeneration" emerge that offers an innovative and exhilarating substitute for maxillofacial reconstruction. It offers a new option to supplement existing treatment regimens for reconstruction/regeneration of the oral and craniofacial complex, which includes the teeth, periodontium, bones, soft tissues (oral mucosa, conjunctiva, skin), salivary glands, and the temporomandibular joint (bone and cartilage), as well as blood vessels, muscles, tendons, and nerves. Tissue engineering is based on harvesting the stem cells which are having potential to form an organ. Harvested cells are then transferred into scaffolds that are manufactured in a laboratory to resemble the structure of the desired tissue to be replaced. This article reviews the principles of tissue engineering and its various applications in oral and maxillofacial surgery.

Unicystic Ameloblastoma of Mandible Treated with an Innovative Approach: A Clinical Case Report.

Ameloblastoma is a true benign neoplasm with its origin from remnants of odontogenic epithelium. Unicystic ameloblastoma presents as a cystic lesion which clinically, radiographically, and macroscopically mimics a mandibular cyst, but microscopically exhibits ameloblastic epithelium lining part of the cyst cavity, with or without intraluminal growth and tumour infiltration into the fibrous connective tissue wall. An important and perplexing aspect associated with ameloblastoma is its management. We hereby present a case of unicystic ameloblastoma in a 63-year-old female and report an innovative technique of treating the case with split iliac crest graft.

Harnessing Next Generation Sequencing in Climate Change: RNA-Seq Analysis of Heat Stress-Responsive Genes in Wheat (Triticum aestivum L.).

Wheat is a staple food worldwide and provides 40% of the calories in the diet. Climate change and global warming pose a threat to wheat production, however, and demand a deeper understanding of how heat stress might impact wheat production and wheat biology. However, it is difficult to identify novel heat stress associated genes when the genomic information is not available. Wheat has a very large and complex genome that is about 37 times the size of the rice genome. The present study sequenced the whole transcriptome of the wheat cv. HD2329 at the flowering stage, under control (22°±3°C) and heat stress (42°C, 2 h) conditions using Illumina HiSeq and Roche GS-FLX 454 platforms. We assembled more than 26.3 and 25.6 million high-quality reads from the control and HS-treated tissues transcriptome sequences respectively. About 76,556 (control) and 54,033 (HS-treated) contigs were assembled and annotated de novo using different assemblers and a total of 21,529 unigenes were obtained. Gene expression profile showed significant differential expression of 1525 transcripts under heat stress, of which 27 transcripts showed very high (>10) fold upregulation. Cellular processes such as metabolic processes, protein phosphorylation, oxidations-reductions, among others were highly influenced by heat stress. In summary, these observations significantly enrich the transcript dataset of wheat available on public domain and show a de novo approach to discover the heat-responsive transcripts of wheat, which can accelerate the progress of wheat stress-genomics as well as the course of wheat breeding programs in the era of climate change.

Awareness and practice concerning oral cancer among Ayurveda and Homeopathy practitioners in Davangere District: A speciality-wise analysis.

CONTEXT: In India, oral cancer accounts for one-third of all cancers. Early detection and immediate intervention can lead to marked reduction in the morbidity and mortality. In India, Ayurveda and homeopathy practitioners are distributed widely in rural and urban areas and are easily accessible. Until date, no assessment on their oral cancer knowledge and practice has been done. AIMS: The present study was undertaken to evaluate the knowledge, awareness, and practice concerning oral cancer. SUBJECTS AND METHODS: Questionnaire comprising 15 questions was distributed to 42 Ayurveda and 38 homeopathy doctors in Davangere District, Karnataka, India, assessing their oral examination habits, knowledge on the risk factors, patient education, clinical signs of the disease and its treatment. STATISTICAL ANALYSIS USED: The results were analyzed using Chi-square test. RESULTS: Lesser number of the practitioners routinely examined oral mucosa (16.7% and 5.3%, respectively). Fewer advised their patients about the risk factors (2.4% and 2.6%). Less positive response was obtained for the correct method for confirmation of diagnosis (28.6% and 15.8%). Many doctors agreed that they had not undergone training in cancer institute (P = 0.29). Twenty-three (54.8%) Ayurveda and 28 (73.7%) homeopathy doctors opined that they did not have sufficient knowledge regarding early detection and prevention of oral cancer and many were desirous of receiving further information (97.6% and 84.2% respectively). CONCLUSIONS: This study attempts to highlight the need for improving the oral cancer knowledge and awareness among practicing Ayurveda and homeopathy doctors.

Changes in the levels of off-flavor generation in soybean through biotic elicitor treatments.

The nutritional benefits of soybean remain underutilized as the off-flavor present in it limits the consumption and acceptability among people. The aim of the present study was to unveil the effect of the phytohormones methyl jasmonate (MJ: 0, 50 µM, 1 mM, and 15 mM) and salicylic acid (SA: 0, 50 µM, 0.1 mM, and 10 mM) as elicitors on two contrasting off-flavor soybean varieties at different growth stages (1, bloom; 2, pod development; 3, seed development). The effects of two elicitors varied widely and were found to be dose dependent and growth stage independent. SA reduces the lipoxygenase (LOX) and hydroperoxide lyase (HPL) activity, which in turn resulted in reduction in the TBA number and carbonyl value in contrast to MJ. SA 0.1 mM is the most effective dose in reduction of off-flavor determining parameters and protein oxidation, and it reduces the LOX and HPL activity by 2.3- and 2.4-fold, respectively in "high off-flavor" cultivar 'Bragg' compared to "low off-flavor" cultivar 'DS 2706' which showed 1.4- and 2.1-fold, respectively. This reduction in protein oxidation is also supported by enhanced content of antioxidant enzymes. Thus, phytohormone SA can be used in reduction of off-flavor generation, more effectively than MJ treatments, in soybean.