Efficacy and safety of emodepside compared with albendazole in adolescents and adults with hookworm infection in Pemba Island, Tanzania: a double-blind, superiority, phase 2b, randomised controlled trial.

BACKGROUND: Human hookworm is a cause of enormous global morbidity. Current treatments have insufficient efficacy and their extensive and indiscriminate distribution could also result in drug resistance. Therefore, we tested the efficacy and safety of emodepside, a strong anthelmintic candidate that is currently undergoing clinical development for onchocerciasis and soil-transmitted helminth infections. METHODS: We conducted a double-blind, superiority, phase 2b, randomised controlled clinical trial comparing emodepside and albendazole. Participants in the emodepside group received six 5 mg tablets of emodepside (totalling 30 mg) and one placebo; participants in the albendazole group received one 400 mg tablet of albendazole and six placebos. Participants were recruited from four endemic villages and three secondary schools in Pemba Island, Tanzania. Participants aged 12-60 years were eligible for treatment if they were positive for hookworm infection, and they had 48 or more eggs per gram from four Kato-Katz thick smears and at least two slides had more than one hookworm egg present. Participants' treatment allocation was stratified by infection intensity and efficacy was measured by cure rate: participants who were hookworm positive and became hookworm negative after treatment. Adverse events were reported at 3 h, 24 h, 48 h, and 14-21 days post-treatment. The trial is registered at ClinicalTrials.gov, NCT05538767. FINDINGS: From Sept 15 to Nov 8, 2022, and from Feb 15 to March 15, 2023, 1609 individuals were screened for hookworm. Of these, 293 individuals were treated: 147 with albendazole and 146 with emodepside. Emodepside demonstrated superiority, with an observed cure rate against hookworm of 96·6%, which was significantly higher compared with albendazole (cure rate 81·2%, odds ratio 0·14, 95% CI 0·04-0·35; p=0·0001). The most common adverse event in the emodepside treatment group was vision blur at 3 h after treatment (57 [39%] of 146). Other common adverse events were vision blur at 24 h after treatment (55 [38%]), and headache and dizziness at 3 h after treatment (55 [38%] for headache and 43 [30%] for dizziness). In the emodepside treatment group, 298 (93%) of the 319 adverse events were mild. The most commonly reported adverse events in the albendazole treatment group were headache and dizziness at 3 h after treatment (27 [18%] of 147 for headache and 14 [10%] for dizziness). No serious adverse events were reported. INTERPRETATION: This phase 2b clinical trial confirms the high efficacy of emodepside against hookworm infections, solidifying emodepside as a promising anthelmintic candidate. However, although the observed safety events were generally mild in severity, considerations must be made to balance the strong efficacy outcomes with the increased frequency of adverse events compared with albendazole. FUNDING: European Research Council.

The importance, benefits, and future of nanobiosensors for infectious diseases.

Infectious diseases, caused by pathogenic microorganisms such as bacteria, viruses, parasites, or fungi, are crucial for efficient disease management, reducing morbidity and mortality rates and controlling disease spread. Traditional laboratory-based diagnostic methods face challenges such as high costs, time consumption, and a lack of trained personnel in resource-poor settings. Diagnostic biosensors have gained momentum as a potential solution, offering advantages such as low cost, high sensitivity, ease of use, and portability. Nanobiosensors are a promising tool for detecting and diagnosing infectious diseases such as coronavirus disease, human immunodeficiency virus, and hepatitis. These sensors use nanostructured carbon nanotubes, graphene, and nanoparticles to detect specific biomarkers or pathogens. They operate through mechanisms like the lateral flow test platform, where a sample containing the biomarker or pathogen is applied to a test strip. If present, the sample binds to specific recognition probes on the strip, indicating a positive result. This binding event is visualized through a colored line. This review discusses the importance, benefits, and potential of nanobiosensors in detecting infectious diseases.

Impact of immunohistochemical expression of kinesin family member 18A (Kif18A) and ß-catenin in infiltrating breast carcinoma of no special type.

BACKGROUND: KIF18A is a regulator of the cell cycle that stimulates the proliferation of cancer cells. The Wnt/ß-catenin pathway is involved in different issues' carcinogenesis and is being examined as a therapeutic target. The relationship between KIF18A and ß-catenin in breast cancer was not previously investigated. Therefore, this work aims to study the immunohistochemical expression and correlation of KIF18A and ß-catenin in breast-infiltrating duct carcinoma (IDC) and their relation to prognosis. MATERIAL AND METHODS: Slides cut from paraffin blocks of 135 IDC and 40 normal breast tissues were stained by KIF18A and ß-catenin antibodies. KIF18A cytoplasmic or nucleocytoplasmic staining and ß-catenin aberrant expression either nucleo-cytoplasmic or cytoplasmic staining were considered. RESULTS: Normal breast tissue and IDC showed a significant difference regarding KIF18A and aberrant ß-catenin expression. High KIF18A and ß-catenin H score values were associated with poor prognostic factors such as high grade, advanced stage, distant metastasis, high Ki67 status, and Her2neu-enriched subtype. There was a significant direct correlation between KIF18A and ß-catenin as regards percent and H score values. Prolonged overall survival (OS) was significantly associated with mild intensity and low H score of KIF18A, and low ß-catenin H score. CONCLUSIONS: KIF18A could be involved in breast carcinogenesis by activating ß-catenin. Overexpression of KIF18A and aberrant expression of ß-catenin are considered proto-oncogenes of breast cancer development. KIF18A and ß-catenin could be poor prognostic markers and predictors of aggressive behavior of breast cancer.

Toll-like receptor 7 and tumor necrosis factor alpha polymorphisms in Egyptian patients with autoimmune thyroid diseases.

Hashimoto's thyroiditis (HT) and Graves' disease (GD) susceptibility depends on a complex interaction between environmental and genetic factors. Genes for tumor necrosis factor alpha (TNF-α) and toll-like receptors (TLRs) have been incorporated into the pathophysiology of autoimmune disorders. Our aim is to assess the association between TLR7 (rs179009) and TNF-α (rs1800629) polymorphisms and susceptibility to autoimmune thyroid disorders. One-hundred ninety-nine individuals, divided into 68 HT patients in group I, 57 GD patients in group II, and 74 age- and gender-matched healthy subjects in group III, underwent laboratory investigations, including the detection of TLR7 and TNF-α polymorphisms using real-time PCR technique. TLR7 (rs179009) genotypes, A/G and G/G, were significantly more prevalent in HT patients (group I) compared to normal controls. Meanwhile, TNF-α (rs1800629) genotypes in GD patients (group II) showed a six fold increase in the risk of the disease in the G/A and A/A genotypes. Our findings propose the fact that the polymorphisms of TLR7 (rs179009) play a role in the susceptibility and the development of Hashimoto's thyroiditis, whereas TNF-α (rs1800629) polymorphisms play a role in the susceptibility and development of Graves' disease.

Asymmetric impact of patents on green technologies on Algeria's Ecological Future.

This study examines how patents on green technologies impact Algeria's ecological footprint from 1990 to 2022 while controlling for economic growth and energy consumption. The objectives are to analyze the asymmetric effects of positive and negative shocks in these drivers on ecological footprint and provide policy insights on leveraging innovations and growth while minimizing environmental harm. Given recent major structural shifts in Algeria's economy, time series data exhibits nonlinear dynamics. To accommodate this nonlinearity, the study employs an innovative nonlinear autoregressive distributed lag approach. The findings indicate that an upsurge in green technologies (termed as a positive shock) significantly reduces the ecological footprint, thereby enhancing ecological sustainability. Interestingly, a decline in green technologies (termed as a negative shock) also contributes to reducing the ecological footprint. This highlights the crucial role of clean technologies in mitigating ecological damage in both scenarios. Conversely, a positive shock in economic growth increases ecological footprint, underscoring the imperative for environmentally friendly policies in tandem with economic expansion. Negative shocks, however, have minimal impact. In a similar vein, positive shock in energy consumption increases ecological footprint, underlining the importance of transitioning towards cleaner energy sources. Negative shock has a smaller but still noticeable effect. The results confirm asymmetric impacts, with positive and negative changes in the drivers affecting Algeria's ecological footprint differently. To ensure long-term economic and ecological stability, Algeria should prioritize eco-innovation and green technology development. This will reduce dependence on fossil fuels and create new, sustainable industries.

Comparative evolutionary analyses of eight whitefly Bemisia tabaci sensu lato genomes: cryptic species, agricultural pests and plant-virus vectors.

BACKGROUND: The group of > 40 cryptic whitefly species called Bemisia tabaci sensu lato are amongst the world's worst agricultural pests and plant-virus vectors. Outbreaks of B. tabaci s.l. and the associated plant-virus diseases continue to contribute to global food insecurity and social instability, particularly in sub-Saharan Africa and Asia. Published B. tabaci s.l. genomes have limited use for studying African cassava B. tabaci SSA1 species, due to the high genetic divergences between them. Genomic annotations presented here were performed using the 'Ensembl gene annotation system', to ensure that comparative analyses and conclusions reflect biological differences, as opposed to arising from different methodologies underpinning transcript model identification. RESULTS: We present here six new B. tabaci s.l. genomes from Africa and Asia, and two re-annotated previously published genomes, to provide evolutionary insights into these globally distributed pests. Genome sizes ranged between 616-658 Mb and exhibited some of the highest coverage of transposable elements reported within Arthropoda. Many fewer total protein coding genes (PCG) were recovered compared to the previously published B. tabaci s.l. genomes and structural annotations generated via the uniform methodology strongly supported a repertoire of between 12.8-13.2 × 103 PCG. An integrative systematics approach incorporating phylogenomic analysis of nuclear and mitochondrial markers supported a monophyletic Aleyrodidae and the basal positioning of B. tabaci Uganda-1 to the sub-Saharan group of species. Reciprocal cross-mating data and the co-cladogenesis pattern of the primary obligate endosymbiont 'Candidatus Portiera aleyrodidarum' from 11 Bemisia genomes further supported the phylogenetic reconstruction to show that African cassava B. tabaci populations consist of just three biological species. We include comparative analyses of gene families related to detoxification, sugar metabolism, vector competency and evaluate the presence and function of horizontally transferred genes, essential for understanding the evolution and unique biology of constituent B. tabaci. s.l species. CONCLUSIONS: These genomic resources have provided new and critical insights into the genetics underlying B. tabaci s.l. biology. They also provide a rich foundation for post-genomic research, including the selection of candidate gene-targets for innovative whitefly and virus-control strategies.

Expression pattern of long non-coding RNAs MALAT1 and MEG3 in COVID-19 patients.

BACKGROUND: COVID-19 is a novel infectious disease for which no specific treatment exists. It is likely that a combination of genetic and non-genetic factors predispose to it. Expression levels of genes that are involved in the interaction with SARS-CoV-2 or the host response are thought to play a role in disease susceptibility and severity. It is crucial to explore biomarkers for disease severity and outcome. Herein, we studied the expression levels and effects of long non-coding metastasis-associated lung adenocarcinoma transcript 1 (lnc-MALAT1) and long non-coding maternally expressed gene 3 (lnc-MEG3) in COVID-19 patients. The study enrolled 35 hospitalized and 35 non-hospitalized COVID-19 patients, and 35 healthy controls. A chest computed tomography (CT) scan, complete blood count (CBC), ferritin, C-reactive protein (CRP), D-dimer and analysis of lnc-MALAT1 and lnc-MEG3 expression were done. RESULTS: There was a significant relation between ferritin, CRP, D-dimer levels, oxygen saturation, CT-CORADS score and disease severity. Lnc-MALAT1 was significantly higher but lnc-MEG3 was significantly lower in patients vs. controls, and in hospitalized vs. non-hospitalized patients. Elevated MALAT1 and reduced MEG3 levels were significantly associated with more elevated ferritin, CRP, D-dimer levels, lower oxygen saturation, higher CT-CORADS score and poor survival. Moreover, MALAT1 and MEG3 levels displayed higher sensitivity and specificity as predictors of COVID-19 severity compared with other prognostic biochemical markers such as ferritin, CRP, and D-dimer. CONCLUSIONS: MALAT1 levels are higher, whereas MEG3 levels are lower in COVID-19 patients. Both are linked to disease severity and mortality and could emerge as predictive biomarkers for COVID-19 severity and therapeutic targets.

Immune profiling of rainbow trout (Oncorhynchus mykiss) exposed to Lactococcus garvieae: Evidence in asymptomatic versus symptomatic or vaccinated fish.

Lactococcosis, caused by the Gram-positive bacterium Lactococcus garvieae, is a major concern in rainbow trout (Oncorhynchus mykiss) farms, which are regularly affected by outbreaks especially during the summer/fall months. In these farms, unvaccinated healthy and symptomatic fish can coexist with vaccinated fish. In the present study, innate (leukogram, serum lysozyme activity, peroxidase activity, antiprotease activity, bactericidal activity, total IgM and total proteins), and specific immune parameters (serum antibodies to L. garvieae) were assessed in unvaccinated adult rainbow trout naturally exposed to the pathogen, with or without evidence of clinical signs, or subjected to vaccination. Blood was drawn from all three groups, and blood smears were prepared. Bacteria were found in the blood smears of 70% of the symptomatic fish but not in any of the asymptomatic fish. Symptomatic fish showed lower blood lymphocytes and higher thrombocytes than asymptomatic fish (p ≤ .05). Serum lysozyme and bactericidal activity did not vary substantially among groups; however, serum antiprotease and peroxidase activity were significantly lower in the unvaccinated symptomatic group than in the unvaccinated and vaccinated asymptomatic groups (p ≤ .05). Serum total proteins and total immunoglobulin (IgM) levels in vaccinated asymptomatic rainbow trout were significantly higher than in unvaccinated asymptomatic and symptomatic groups (p ≤ .05). Similarly, vaccinated asymptomatic fish produced more specific IgM against L. garvieae than unvaccinated asymptomatic and symptomatic fish (p ≤ .05). This preliminary study provides basic knowledge on the immunological relationship occurring between the rainbow trout and L. garvieae, potentially predicting health outcomes. The approach we proposed could facilitate infield diagnostics, and several non-specific immunological markers could serve as reliable indicators of the trout's innate ability to fight infection.

Structural Diversity, Spectral Data, and Pharmacological Effects of Genus Nigella.

Nigella is one of the most studied plants because of its pharmacological properties like anti-parasitic, anti-inflammatory, neuro-protective, hepatoprotective, and anti-cancerous. In this study, about 20 species of the genus Nigella were reviewed and among them, N. damascene, N. glandulifera, and N. sativa are widely studied for their phytochemical and pharmacological effects. This review describes the phytochemical composition of the genus Nigella, which constitutes many of the compounds including alkaloids, flavonoids, saponins, and terpenoids. The extracts produced by using different solvents and the isolated compounds displayed a wide range of biological activity. These compounds were identified by different spectral techniques. The spectral detail of some advanced techniques including EIS-MS, UV/VIS, IR, 13 C-NMR, and 1 H-NMR of some important phytoconstituents of Nigella spp. has been compiled for the first time in this review which will be helpful to explore and further investigate the chemical composition of this genus.

Longitudinal Studies of Wearables in Patients with Diabetes: Key Issues and Solutions.

Glucose monitoring is key to the management of diabetes mellitus to maintain optimal glucose control whilst avoiding hypoglycemia. Non-invasive continuous glucose monitoring techniques have evolved considerably to replace finger prick testing, but still require sensor insertion. Physiological variables, such as heart rate and pulse pressure, change with blood glucose, especially during hypoglycemia, and could be used to predict hypoglycemia. To validate this approach, clinical studies that contemporaneously acquire physiological and continuous glucose variables are required. In this work, we provide insights from a clinical study undertaken to study the relationship between physiological variables obtained from a number of wearables and glucose levels. The clinical study included three screening tests to assess neuropathy and acquired data using wearable devices from 60 participants for four days. We highlight the challenges and provide recommendations to mitigate issues that may impact the validity of data capture to enable a valid interpretation of the outcomes.

Examining the Effect of an Educational Program on Nursing Students' Informatics Competencies.

ABSTRACT: This study aimed to determine the effect of a two-day education program on the informatics competencies of undergraduate nursing students. A one-group pretest-posttest design was employed using a convenience sample of 83 students. SANICS-18 (Self-Assessment of Nursing Informatics Competencies Scale) items were used to measure nursing informatics competencies. The pretest findings indicated a low overall score for nursing informatics competencies, with applied computer skills being the lowest self-reported competency subscale (clinical informatics). Following implementation of the education program, nursing students' general informatics competencies improved. The findings suggest that nursing programs should provide continuing nursing informatics training and integrate skills and competencies within the nursing curriculum.

Artificial Intelligence and Its Application in Endodontics: A Review.

AIM AND BACKGROUND: Artificial intelligence (AI) since it was introduced into dentistry, has become an important and valuable tool in many fields. It was applied in different specialties with different uses, for example, in diagnosis of oral cancer, periodontal disease and dental caries, and in the treatment planning and predicting the outcome of orthognathic surgeries. The aim of this comprehensive review is to report on the application and performance of AI models designed for application in the field of endodontics. MATERIALS AND METHODS: PubMed, Web of Science, and Google Scholar were searched to collect the most relevant articles using terms, such as AI, endodontics, and dentistry. This review included 56 papers related to AI and its application in endodontics. RESULT: The applications of AI were in detecting and diagnosing periapical lesions, assessing root fractures, working length determination, prediction for postoperative pain, studying root canal anatomy and decision-making in endodontics for retreatment. The accuracy of AI in performing these tasks can reach up to 90%. CONCLUSION: Artificial intelligence has valuable applications in the field of modern endodontics with promising results. Larger and multicenter data sets can give external validity to the AI models. CLINICAL SIGNIFICANCE: In the field of dentistry, AI models are specifically crafted to contribute to the diagnosis of oral diseases, ranging from common issues such as dental caries to more complex conditions like periodontal diseases and oral cancer. AI models can help in diagnosis, treatment planning, and in patient management in endodontics. Along with the modern tools like cone-beam computed tomography (CBCT), AI can be a valuable aid to the clinician. How to cite this article: Ahmed ZH, Almuharib AM, Abdulkarim AA, et al. Artificial Intelligence and Its Application in Endodontics: A Review. J Contemp Dent Pract 2023;24(11):912-917.

Cardiovascular and haematological events post COVID-19 vaccination: A systematic review.

Since COVID-19 took a strong hold around the globe causing considerable morbidity and mortality, a lot of effort was dedicated to manufacturing effective vaccines against SARS-CoV-2. Many questions have since been raised surrounding the safety of the vaccines, and a lot of media attention to certain side effects. This caused a state of vaccine hesitancy that may prove problematic in the global effort to control the virus. This review was undertaken with the aim of putting together all the reported cardiovascular and haematological events post COVID-19 vaccination in published literature and to suggest possible mechanisms to explain these rare phenomena.

The motives, academic performance, and career prospects of Gazan medical students abroad: a cross-sectional study.

BACKGROUND: In Gaza, 2 million people have been affected by more than 13 years of strict land, air, and sea blockades and three wars, during which over 4000 people have been killed and many more have been injured. Additional severe effects have been seen on lives, aspirations, and prospects. Given the conditions, medical students have many competing reasons for and against studying medicine abroad. We investigated motives, academic situations, and future plans of the upcoming generation of doctors in Gaza, occupied Palestinian territory. METHODS: We did a questionnaire-based cross-sectional study involving Palestinian medical students originally from Gaza who were studying at the largest five medical schools in Egypt (Cairo, Ain Shams, Alexandria, Mansoura, and Zagazig Universities). We used a self-designed questionnaire developed from previous similar studies and created on Google Forms (Google, Menlo Park, CA, USA). A pilot study of 37 participants was done to test the comprehensibility of questions and the time needed to complete the questionnaire. After being updated, the questionnaire was distributed in August and September, 2018, to individuals who provided verbal informed decision to participate. Analysis of the results was performed with SPSS version 22. FINDINGS: Of 453 questionnaires given to students, 340 (75%) were returned completed. The mean age of respondents was 21·7 (SD 1·8) years; 225 (66%) were men and 115 (34%) were women. Excellence was achieved in secondary school examinations (result ≥90%) by 315 (93%) of students, but only 26 (8%) of students achieved excellence in their first year of medical school (examination results ≥85%). 317 students (93%) reported that they chose their medical schools independently without pressure from their families. Among the 115 women, 70 (61%) went to a third party to persuade their parents to allow them to study abroad. Of ten motives to study medicine given in the questionnaire, "to relieve pains" and "childhood dream" were the most frequently selected among the 340 respondents, chosen by 228 (67%) and 208 (61%), respectively. 104 (31%) reported they were seeking freedom more than to study medicine. 214 (63%) of students had at least one relative who had been physically injured in or killed during of one of the wars in Gaza. Most students (n=278 [82%]) were delayed from starting at their medical school due to border closures and 189 (56%) had been unable to attend for at least one semester. Since starting at medical school, 269 (79%) of 340 respondents had visited Gaza only once or not at all. 55 (16%) intended never return to Gaza and 209 (62%) reported that they wanted to specialise and work abroad for a period and then return to Gaza. Of the remainder, 64 (19%) wanted to specialise abroad then return to work in Gaza, and 12 (3%) wanted to specialise and work in Gaza. INTERPRETATION: The motives, academic performance, and career prospects of Gazan medical students studying in Egypt are influenced in many ways by the situation in Gaza, some of which could worsen the already bad condition of medical care in Gaza. Awareness and supportive programmes for Gazan medical students should be encouraged to improve the quality of health care providers in Gaza. FUNDING: None.

Lymphadenopathy post-COVID-19 vaccination with increased FDG uptake may be falsely attributed to oncological disorders: A systematic review.

Coronavirus disease 2019 (COVID-19) has caused a global pandemic that continues to cause numerous deaths to date. Four vaccines have been approved by the Food and Drug Administration as of July 2021 to prevent the transmission of COVID-19: Pfizer, Moderna, AstraZeneca, and Janssen. These vaccines have shown great efficacy and safety profile. One side effect that has been widely reported is post-COVID-19 vaccination lymphadenopathy. Due to the mimicry of the lymphadenopathy for metastases in some oncologic patients, there have been reports of patients who underwent biopsies that showed pathologic confirmation of benign reactive lymphadenopathy secondary to the COVID-19 vaccine. Therefore, understanding the incidence of lymphadenopathy post-COVID-19 vaccinations will help guide radiologists and oncologists in their management of patients, both present oncologic patients, and patients with concerns over their newly presenting lymphadenopathy. A systematic literature search was performed using several databases to identify relevant studies that reported lymphadenopathy post-COVID-19 vaccination. Our results revealed that several cases have been detected in patients undergoing follow-up fluorodeoxyglucose (FDG)-positron emission tomography-computerized tomography scans where lymph nodes ipsilateral to the vaccine injection site show increased uptake of FDG. Thus, knowledge of the incidence of lymphadenopathy may help avoid unnecessary biopsies, interventions, and changes in management for patients, especially oncologic patients who are at risk for malignancies.

Association between dietary total antioxidant capacity and hypertension in Iranian Kurdish women.

BACKGROUND: Antioxidants intake from diet has been identified as one of the effective factors in the development of hypertension (HTN). The present study aimed to investigate the association between total antioxidant capacity (TAC) and HTN in women. METHODS: This cross-sectional study was performed using the baseline phase data of the ravansar non-communicable disease cohort study. The TAC was calculated using food items of the food frequency questionnaire. TAC scores were classified into four groups (quartile). The first and fourth quartiles had the lowest and highest TAC scores, respectively. Logistic regression analysis was utilized to estimate the odds ratio. RESULTS: A total of 5067 women were included in the study. Women with the highest socioeconomic status (SES) had a significantly higher TAC intake compared to those with the lowest SES (P < 0.001). The participants in the third and fourth quartiles of the TAC had significantly lower odds of HTN, respectively by 21% (OR = 0.79; 95% CI: 0.64, 0.972) and 26% (OR = 0.74; 95% CI: 0.60, 0.91), compared to the first quartile. After adjusting for confounding variables was found to significantly reduce the odds of developing HTN in the fourth quartile of TAC by 22% compared to the first quartile (OR = 0.78; 95% CI: 0.62, 0.97). CONCLUSION: A high dietary TAC was associated to a decreased odd of HTN in women. We could suggest a diet rich in natural antioxidants as it may help prevent development of HTN.

Variant analyses of candidate genes in orofacial clefts in multi-ethnic populations.

OBJECTIVES: Cleft lip with/without cleft palate and cleft palate only is congenital birth defects where the upper lip and/or palate fail to fuse properly during embryonic facial development. Affecting ~1.2/1000 live births worldwide, these orofacial clefts impose significant social and financial burdens on affected individuals and their families. Orofacial clefts have a complex etiology resulting from genetic variants combined with environmental covariates. Recent genome-wide association studies and whole-exome sequencing for orofacial clefts identified significant genetic associations and variants in several genes. Of these, we investigated the role of common/rare variants in SHH, RORA, MRPL53, ACVR1, and GDF11. MATERIALS AND METHODS: We sequenced these five genes in 1255 multi-ethnic cleft lip with/without palate and cleft palate only samples in order to find variants that may provide potential explanations for the missing heritability of orofacial clefts. Rare and novel variants were further analyzed using in silico predictive tools. RESULTS: Ninteen total variants of interest were found, with variant types including stop-gain, missense, synonymous, intronic, and splice-site variants. Of these, 3 novel missense variants were found, one in SHH, one in RORA, and one in GDF11. CONCLUSION: This study provides evidence that variants in SHH, RORA, MRPL53, ACVR1, and GDF11 may contribute to risk of orofacial clefts in various populations.

Elucidating the Role of Santalol as a Potent Inhibitor of Tyrosinase: In Vitro and In Silico Approaches.

This research work focuses on the potential application of an organic compound, santalol, obtained from santalum album, in the inhibition of the enzyme tyrosinase, which is actively involved in the biosynthesis of melanin pigment. Over-production of melanin causes undesirable pigmentation in humans as well as other organisms and significantly downgrades their aesthetic value. The study is designed to explain the purification of tyrosinase from the mushroom Agaricus bisporus, followed by activity assays and enzyme kinetics to give insight into the santalol-modulated tyrosinase inhibition in a dose-dependent manner. The multi-spectroscopic techniques such as UV-vis, fluorescence, and isothermal calorimetry are employed to deduce the efficiency of santalol as a potential candidate against tyrosinase enzyme activity. Experimental results are further verified by molecular docking. Santalol, derived from the essential oils of santalum album, has been widely used as a remedy for skin disorders and a potion for a fair complexion since ancient times. Based on enzyme kinetics and biophysical characterization, this is the first scientific evidence where santalol inhibits tyrosinase, and santalol may be employed in the agriculture, food, and cosmetic industries to prevent excess melanin formation or browning.

Preparation, characterization, in vitro drug release and anti-inflammatory of thymoquinone-loaded chitosan nanocomposite.

In this study, we formulated Thymoquinone-loaded nanocomposites (TQ-NCs) using high-pressure homogenizer without sodium tripolyphosphate. The TQ-NCs were characterized and their anti-inflammatory determined by the response of the LPS-stimulated macrophage RAW 264.7 cells in the production of nitric oxide, prostaglandin E2, tumor necrosis factor-α, interleukin-6, and interleukin-1ß. The physicochemical properties of TQ-NC were determined using different machines. TQ was fully incorporated in the highly thermal stable nanoparticles. The nanoparticles showed rapid release of TQ in the acidic medium of the gastric juice. In medium of pH 6.8, TQ-NC exhibited sustained release of TQ over a period of 100 h. The results suggest that TQ-NC nanoparticles have potential application as parenterally administered therapeutic compound. TQ-NC effectively reduce production of inflammatory cytokines by the LPS-stimulated RAW 264.7 cells, indicating that they have anti-inflammatory properties. In conclusion, TQ-NC nanoparticles have the characteristics of efficient carrier for TQ and an effective anti-inflammatory therapeutic compound.

The utility of c-Met as a diagnostic tissue biomarker in primary colorectal cancer.

The transmembrane protein, c-Met, is thought to be overexpressed and activated in colorectal cancer (CRC). This study explored its potential as a diagnostic tissue biomarker for CRC in a large human CRC tissue collection obtained from a randomized clinical trial. Tissue microarrays of matched normal colorectal epithelium and primary cancer were prepared from specimens obtained from 280 patients recruited to the MRC CLASICC trial (ISRCTN 74883561) and interrogated using immunohistochemistry for c-Met expression. The distribution and intensity of immunopositivity was graded using a validated, semi-quantifiable score, and differences in median scores analysed using the Wilcoxon signed-rank test. A receiver operating characteristic (ROC) curve was plotted to measure the diagnostic accuracy of c-Met as a biomarker in CRC. Epithelial cell membrane expression of c-Met differed significantly between CRC and normal colorectal tissue: median 12.00 (Interquartile range (IQR) 6-15) versus median 6.00 (IQR 2.70-12.00) respectively (P = <.0001). ROC-AUC analysis of c-Met expression yielded a CRC diagnostic probability of 0.66 (95% CI: 0.61 to 0.70; P < .0001). A score of ≥14.50 showed high specificity at 85.32% (95% CI 80.33%-89.45%) but sensitivity of only 30.92% (CI 25.37%-36.90%). Thus c-Met is consistently overexpressed in human CRC as compared to normal colorectal epithelium tissue. c-Met expression may have a role in diagnosis and prognostication if combined with other biomarkers.