Narrative review on nanoparticles based on current evidence: therapeutic agents for diabetic foot infection.

Diabetes's effects on wound healing present a major treatment challenge and increase the risk of amputation. When traditional therapies fail, new approaches must be investigated. With their submicron size and improved cellular internalisation, nanoparticles present a viable way to improve diabetic wound healing. They are attractive options because of their innate antibacterial qualities, biocompatibility, and biodegradability. Nanoparticles loaded with organic or inorganic compounds, or embedded in biomimetic matrices such as hydrogels, chitosan, and hyaluronic acid, exhibit excellent anti-inflammatory, antibacterial, and antioxidant properties. Drug delivery systems (DDSs)-more precisely, nanodrug delivery systems (NDDSs)-use the advantages of nanotechnology to get around some of the drawbacks of traditional DDSs. Recent developments show how expertly designed nanocarriers can carry a variety of chemicals, transforming the treatment of diabetic wounds. Biomaterials that deliver customised medications to the wound microenvironment demonstrate potential. Delivery techniques for nanomedicines become more potent than ever, overcoming conventional constraints. Therapeutics for diabetes-induced non-healing wounds are entering a revolutionary era thanks to precisely calibrated nanocarriers that effectively distribute chemicals. This review highlights the therapeutic potential of nanoparticles and outlines the multifunctional nanoparticles of the future that will be used for complete wound healing in diabetics. The investigation of novel nanodrug delivery systems has the potential to revolutionise diabetic wound therapy and provide hope for more efficient and focused therapeutic approaches.

IDHwt glioblastomas can be stratified by their transcriptional response to standard treatment, with implications for targeted therapy.

BACKGROUND: Glioblastoma (GBM) brain tumors lacking IDH1 mutations (IDHwt) have the worst prognosis of all brain neoplasms. Patients receive surgery and chemoradiotherapy but tumors almost always fatally recur. RESULTS: Using RNA sequencing data from 107 pairs of pre- and post-standard treatment locally recurrent IDHwt GBM tumors, we identify two responder subtypes based on longitudinal changes in gene expression. In two thirds of patients, a specific subset of genes is upregulated from primary to recurrence (Up responders), and in one third, the same genes are downregulated (Down responders), specifically in neoplastic cells. Characterization of the responder subtypes indicates subtype-specific adaptive treatment resistance mechanisms that are associated with distinct changes in the tumor microenvironment. In Up responders, recurrent tumors are enriched in quiescent proneural GBM stem cells and differentiated neoplastic cells, with increased interaction with the surrounding normal brain and neurotransmitter signaling, whereas Down responders commonly undergo mesenchymal transition. ChIP-sequencing data from longitudinal GBM tumors suggests that the observed transcriptional reprogramming could be driven by Polycomb-based chromatin remodeling rather than DNA methylation. CONCLUSIONS: We show that the responder subtype is cancer-cell intrinsic, recapitulated in in vitro GBM cell models, and influenced by the presence of the tumor microenvironment. Stratifying GBM tumors by responder subtype may lead to more effective treatment.

iSCORE-PD: an isogenic stem cell collection to research Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder caused by complex genetic and environmental factors. Genome-edited human pluripotent stem cells (hPSCs) offer the uniique potential to advance our understanding of PD etiology by providing disease-relevant cell-types carrying patient mutations along with isogenic control cells. To facilitate this experimental approach, we generated a collection of 55 cell lines genetically engineered to harbor mutations in genes associated with monogenic PD (SNCA A53T, SNCA A30P, PRKN Ex3del, PINK1 Q129X, DJ1/PARK7 Ex1-5del, LRRK2 G2019S, ATP13A2 FS, FBXO7 R498X/FS, DNAJC6 c.801 A>G+FS, SYNJ1 R258Q/FS, VPS13C A444P, VPS13C W395C, GBA1 IVS2+1). All mutations were generated in a fully characterized and sequenced female human embryonic stem cell (hESC) line (WIBR3; NIH approval number NIHhESC-10-0079) using CRISPR/Cas9 or prime editing-based approaches. We implemented rigorous quality controls, including high density genotyping to detect structural variants and confirm the genomic integrity of each cell line. This systematic approach ensures the high quality of our stem cell collection, highlights differences between conventional CRISPR/Cas9 and prime editing and provides a roadmap for how to generate gene-edited hPSCs collections at scale in an academic setting. We expect that our isogenic stem cell collection will become an accessible platform for the study of PD, which can be used by investigators to understand the molecular pathophysiology of PD in a human cellular setting.

Assessment of Knowledge and Attitude Toward Pelvic Inflammatory Disease Among Women in Saudi Arabia.

Purpose Pelvic inflammatory disease (PID) is a serious infection of the female reproductive system that can lead to long-term complications such as infertility, chronic pelvic pain, and ectopic pregnancy. PID is also associated with an increased risk of HIV infection and other sexually transmitted infections (STIs). Early diagnosis and treatment of PID is crucial to prevent complications. Despite the severe consequences of PID, many women are unaware of the risks associated with this condition. This lack of awareness can lead to delayed diagnosis and treatment, increasing the risk of complications. This study explores women's knowledge and attitudes regarding PID. Methods A cross-sectional survey was conducted using a bilingual, community-based questionnaire, circulated using different social media platforms. A total of 239 participants were selected through convenient non-probability sampling from the public in the Kingdom of Saudi Arabia. The collected data was analyzed using SPSS Statistics version 26 (IBM Corp. Released 2019. IBM SPSS Statistics for Windows, Version 26.0. Armonk, NY: IBM Corp.). The chi-square test was applied to determine the differences between knowledge and attitude levels with participants' socio-demographic characteristics. A p-value <0.005 was considered statistically significant. Results Appropriate PID knowledge level was found only in 32% of the respondents and was significantly associated with the respondents' family history of the PID (p=0.025). A positive attitude toward PID/STI was also observed only in 36% of the study participants, which was significantly associated with the respondents' age (p˂0.001), marital status (p˂0.001), occupation (p˂ 0.001), past medical/surgical history (p=0.006), and family history of the PID (p˂0.009). Conclusion The present study reported average levels of appropriate knowledge and attitudes toward PID among female respondents, which could be further improved by increasing PID/STI awareness programs.

Sampling Methods and their Prospects in Liquid-Based Cytology of Oral Mucosa: A Comparative Study.

Examining epithelial cells in the mouth cavity is simple and non-invasive with exfoliative cytology. Liquid-based cytology is an additional diagnostic technique that can improve the specificity and sensitivity of conventional cytology. The purpose of our study was to describe the consistency of normal oral mucosa samples obtained with three different tools: the Cytobrush®, dermatological curette, and OralCDx® for liquid-based cytology. Literature review was done, and reporting of the improvements in the field of investigation and diagnosis has been reported. The present communication aims toward comparing three different sampling instruments such as Cytobrush, curette, and OralCDx for liquid-based cytology of the oral mucosa.

Community-Acquired Methicillin-Resistant Staphylococcus aureus in Hospitals: Age-Specificity and Potential Zoonotic-Zooanthroponotic Transmission Dynamics.

Methicillin-resistant Staphylococcus aureus (MRSA) lineages are a devastating clinical and public health issue. Data on local lineage profiles are limited. We report on the frequency of community-acquired and hospital-acquired cases (CA-MRSA, HA-MRSA). We studied 147 isolates from King Khalid tertiary care hospitals (KKH), each from a case in a patient and including 33 patients at the Maternity and Children's Hospital (MCH). Of the 147 isolates, 87 males (59%) and 60 females (41%) were in KKH. The overwhelming majority (80%; n = 119/147) were CA-MRSA in KKH. Intriguingly, despite significant differences between males (70%) and females (53%), lineage-acquisition remained age-specific around 58-60 years in both genders. However, while CA-MRSA dominated early in life (0-20, 70% MCH), it increased with age in KKH adults; 21-50 (28%), >50 (59%) until the overall 80% (n = 144/180). Major specimens included skin-wounds, surgeries (70.3%), blood (13.5%), sputum (8.8%), very rarely urine (4.1%), and nasal (3.4%), albeit most patients showed severe enteritis and necrotizing pneumonia. Antibiograms showed high beta lactam resistances, including amoxicillin-clavulanate (83%), oxacillin (84%), cefoxitin FOX (100%), penicillin and ampicillin (~100%), as well as high resistance (82%) to carbapenem. Fortunately, high susceptibility was seen to non-beta lactams and, to a lesser extent, gentamicin, erythromycin, and fusidic acid; 33%, 34%, and 38%, respectively, in KKH. A similar pattern was seen in MCH except for a low resistance pattern to gentamicin CN, clindamycin CD, erythromycin E, and tobramycin TOB; 34%, 31%, 39%, and 41%, respectively, except for fusidic acid. These findings have significant clinical implications for MRSA patient management strategies. Clinical- and lineage-profiles imply host-selection and zoonotic-zooanthroponotic transmission dynamics. Future molecular typing, sequencing, and characterization of dominant clone(s) is imperative.

A Sequalae of Lineage Divergence in Staphylococcus aureus from Community-Acquired Patterns in Youth to Hospital-Associated Profiles in Seniors Implied Age-Specific Host-Selection from a Common Ancestor.

The rapidly changing epidemiology of Staphylococcus aureus and evolution of strains with enhanced virulence is a significant issue in global healthcare. Hospital-associated methicillin-resistant S. aureus (HA-MRSA) lineages are being completely replaced by community-associated S. aureus (CA-MRSA) in many regions. Surveillance programs tracing the reservoirs and sources of infections are needed. Using molecular diagnostics, antibiograms, and patient demographics, we have examined the distributions of S. aureus in Ha'il hospitals. Out of 274 S. aureus isolates recovered from clinical specimens, 181 (66%, n = 181) were MRSA, some with HA-MRSA patterns across 26 antimicrobials with almost full resistances to all beta-lactams, while the majority were highly susceptible to all non-beta-lactams, indicating the CA-MRSA type. The rest of isolates (34%, n = 93) were methicillin-susceptible, penicillin-resistant MSSA lineages (90%). The MRSA in men was over 56% among total MRSA (n = 181) isolates and 37% of overall isolates (n = 102 of 274) compared to MSSA in total isolates (17.5%, n = 48), respectively. However, these were 28.4% (n = 78) and 12.4% (n = 34) for MRSA and MSSA infections in women, respectively. MRSA rates per age groups of 0-20, 21-50, and >50 years of age were 15% (n = 42), 17% (n = 48), and 32% (n = 89), respectively. However, MSSA in the same age groups were 13% (n = 35), 9% (n = 25), and 8% (n = 22). Interestingly, MRSA increased proportional to age, while MSSA concomitantly decreased, implying dominance of the latter ancestors early in life and then gradual replacement by MRSA. The dominance and seriousness of MRSA despite enormous efforts in place is potentially for the increased use of beta-lactams known to enhance virulence. The Intriguing prevalence of the CA-MRSA patterns in young otherwise healthy individuals replaced by MRSA later in seniors and the dominance of penicillin-resistant MSSA phenotypes imply three types of host- and age-specific evolutionary lineages. Thus, the decreasing MSSA trend by age with concomitant increase and sub-clonal differentiation into HA-MRSA in seniors and CA-MRSA in young and otherwise healthy patients strongly support the notion of subclinal emergences from a resident penicillin-resistant MSSA ancestor. Future vertical studies should focus on the surveillance of invasive CA-MRSA rates and phenotypes.

Pathogen Burden Among ICU Patients in a Tertiary Care Hospital in Hail Saudi Arabia with Particular Reference to ß-Lactamases Profile.

Purpose: Ventilator-associated pneumonia (VAP) is associated with a higher mortality risk for critical patients in the intensive care unit (ICU). Several strategies, including using ß-lactam antibiotics, have been employed to prevent VAP in the ICU. However, the lack of a gold-standard method for VAP diagnosis and a rise in antibiotic-resistant microorganisms have posed challenges in managing VAP. The present study is designed to identify, characterize, and perform antimicrobial susceptibility of the microorganisms from different clinical types of infections in ICU patients with emphasis on VAP patients to understand the frequency of the latter, among others. Patients and Methods: A 1-year prospective study was carried out on patients in the ICU unit at a tertiary care hospital, Hail, Saudi Arabia. Results: A total of 591 clinically suspected hospital-acquired infections (HAI) were investigated, and a total of 163 bacterial isolates were obtained from different clinical specimens with a high proportion of bacteria found associated with VAP (70, 43%), followed by CAUTI (39, 24%), CLABSI (25, 15%), and SSI (14, 8.6%). Klebsiella pneumoniae was the most common isolate 39 (24%), followed by Acinetobacter baumannii 35 (21.5%), Pseudomonas aeruginosa 25 (15.3%), and Proteus spp 23 (14%). Among the highly prevalent bacterial isolates, extended-spectrum beta-lactamase was predominant 42 (42.4%). Conclusion: Proper use of antibiotics, continuous monitoring of drug sensitivity patterns, and taking all precautionary measures to prevent beta-lactamase-producing organisms in clinical settings are crucial and significant factors in fending off life-threatening infections for a better outcome.

Molecular Characterization and Antibiogram of Acinetobacter baumannii Clinical Isolates Recovered from the Patients with Ventilator-Associated Pneumonia.

A 2-year prospective study carried out on ventilator-associated pneumonia (VAP) patients in the intensive care unit at a tertiary care hospital, Hail, Kingdom of Saudi Arabia (KSA), revealed a high prevalence of extremely drug-resistant (XDR) Acinetobacter baumannii. About a 9% increase in the incidence rate of A. baumannii occurred in the VAP patients between 2019 and 2020 (21.4% to 30.7%). In 2019, the isolates were positive for IMP-1 and VIM-2 (31.1% and 25.7%, respectively) as detected by PCR. In comparison, a higher proportion of isolates produced NDM-1 in 2020. Here, we observed a high proportion of resistant ICU isolates towards the most common antibiotics in use. Colistin sensitivity dropped to 91.4% in the year 2020 as compared to 2019 (100%). Thus, the finding of this study has a highly significant clinical implementation in the clinical management strategies for VAP patients. Furthermore, strict implementation of antibiotic stewardship policies, regular surveillance programs for antimicrobial resistance monitoring, and screening for genes encoding drug resistance phenotypes have become imperative.

Highly efficient generation of isogenic pluripotent stem cell models using prime editing.

The recent development of prime editing (PE) genome engineering technologies has the potential to significantly simplify the generation of human pluripotent stem cell (hPSC)-based disease models. PE is a multicomponent editing system that uses a Cas9-nickase fused to a reverse transcriptase (nCas9-RT) and an extended PE guide RNA (pegRNA). Once reverse transcribed, the pegRNA extension functions as a repair template to introduce precise designer mutations at the target site. Here, we systematically compared the editing efficiencies of PE to conventional gene editing methods in hPSCs. This analysis revealed that PE is overall more efficient and precise than homology-directed repair of site-specific nuclease-induced double-strand breaks. Specifically, PE is more effective in generating heterozygous editing events to create autosomal dominant disease-associated mutations. By stably integrating the nCas9-RT into hPSCs we achieved editing efficiencies equal to those reported for cancer cells, suggesting that the expression of the PE components, rather than cell-intrinsic features, limit PE in hPSCs. To improve the efficiency of PE in hPSCs, we optimized the delivery modalities for the PE components. Delivery of the nCas9-RT as mRNA combined with synthetically generated, chemically-modified pegRNAs and nicking guide RNAs improved editing efficiencies up to 13-fold compared with transfecting the PE components as plasmids or ribonucleoprotein particles. Finally, we demonstrated that this mRNA-based delivery approach can be used repeatedly to yield editing efficiencies exceeding 60% and to correct or introduce familial mutations causing Parkinson's disease in hPSCs.

From muscles to nerves, our body is formed of many kinds of cells which can each respond slightly differently to the same harmful genetic changes. Understanding the exact relationship between mutations and cell-type specific function is essential to better grasp how conditions such as Parkinson's disease or amyotrophic lateral sclerosis progress and can be treated. Stem cells could be an important tool in that effort, as they can be directed to mature into many cell types in the laboratory. Yet it remains difficult to precisely introduce disease-relevant mutations in these cells. To remove this obstacle, Li et al. focused on prime editing, a cutting-edge 'search and replace' approach which can introduce new genetic information into a specific DNA sequence. However, it was unclear whether this technique could be used to efficiently create stem cell models of human diseases. A first set of experiments showed that prime editing is superior to conventional approaches when generating mutated genes in stem cells. Li et al. then further improved the efficiency and precision of the method by tweaking how prime editing components are delivered into the cells. The refined approach could be harnessed to quickly generate large numbers of stem cells carrying mutations associated with Parkinson's disease; crucially, prime editing could then also be used to revert a mutated gene back to its healthy form. The improved prime editing approach developed by Li et al. removes a major hurdle for scientists hoping to use stem cells to study genetic diseases. This could potentially help to unlock progress in how we understand and ultimately treat these conditions.

Antiglycation potential of plant based TiO2 nanoparticle in D-ribose glycated BSA in vitro.

Biosynthetic procedure is one of the best alternatives, inexpensive and ecologically sound for the synthesis of titanium dioxide (TiO2 ) nanoparticles using a methanolic extract of medicinal plant. The main prospect of this study was to investigate the antiglycation activity of the TiO2 nanoparticles (TNP) prepared by ethanolic leaf extract of the Coleus scutellarioides. In this study, biosynthesized TNP characterized with UV-Visible spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy and scanning electron microscope. These TNP were further investigated with respect to their antiglycation property and it was checked in the mixture of d-ribose glycated bovine serum albumin (BSA) by measuring ketoamine, carbonyl content, Advanced glycation end products (AGEs) and aggregation of protein instigated by glycation process. The inhibitory effect of TNP to restore the structure of BSA in presence of d-ribose were also characterize by biophysical techniques mentioned above. Therefore, the findings of this study suggest repurposing of TNP for its antiglycation property that could be helpful in prevention of glycation instigated AGEs formation and structural loss of proteins.

Glycation of Immunoglobulin-G from Pentose Sugar: A Cause for Structural Perturbations.

BACKGROUND: Glycation of immunoglobulin-G (IgG) molecules with monosaccharides may cause significant structural disability, thus resulting in their loss of function. The accumulation of AGEs formed from glycation plays an important role in the aliments associated with metabolic diseases. Therefore, excess sugar in plasma interferes with the functioning of IgG and may contribute to a wide range of diabetes-associated complications. The long-term formation of these heterogeneous AGEs may accumulate and affect plasma proteins, especially long-lived proteins. In this study, we analyze immunoglobulin-G (IgG) glycation with 2'-deoxyribose (deoxyribose) instigated modification in IgG structure and AGEs formation. METHODS: This study aims to glycate IgG from varying concentrations of pentose sugar, 2'-deoxyribose (deoxyribose). Various physicochemical methods and techniques characterized post glycation of IgG, both the native and its glycated analogue. The glycated protein will be assessed for its stability and perturbations by UV-VIS., fluorescence and FT-IR spectroscopic techniques. Moreover, the early glycation product will be done by NBT assay, and other biochemical parameters like HMF, carbonyl content and thioflavin-T assays were also performed to see the biochemical changes induced in the glycated IgG macromolecule. RESULTS: Glycation of protein macromolecules generates stable early glycation products (Amadori products). Later, these Amadori products involved a series of chemical reactions to form more stable advanced glycation end products (AGEs). Our experimental study results could validate the modification in IgG structure and AGEs formation. CONCLUSION: The formation of IgG-AGEs from glycation of IgG with deoxyribose could exert cellular toxicity, and might initiates secondary complications of diabetes. Therefore, this study emphasized the glycation reaction of IgG from deoxyribose, which has not been reported yet.

Catheter-Associated Urinary Tract Infection in Intensive Care Unit Patients at a Tertiary Care Hospital, Hail, Kingdom of Saudi Arabia.

Catheter-associated urinary tract infections (CAUTIs) are some of the most common hospital-acquired infections (HAIs). Prolonged hospitalization, invasive devices such as catheters, and irrational use of antimicrobial agents are believed to be the major causes of high rates of HAIs. Infections such as pyelonephritis, urethritis, cystitis, and prostatitis are the main concerns in catheterized ICU patients. In these cases, Gram-negative bacteria are the most common bacteria. The present study was undertaken to determine the frequency, antibiograms, disease pattern, and risk factors involved in providing an advocacy recommendation to prevent CAUTI. A total of 1078 patients were admitted to the hospital ICU, out of which healthcare-associated infection was reported in 316 patients. CAUTI was reported only in 70 patients. Klebsiella pneumoniae (20%) was the predominant isolate, with Serratia (3%) and Providencia (3%) species being the least common isolates in this study. The present study provides CAUTI incidence rates in a tertiary care hospital in Hail, Saudi Arabia. Furthermore, information on the risk factors of common associated CAUTI causative organisms and their antibiogram patterns are also presented. This study provides vital information that can be used to formulate an effective antibiotic stewardship program that can be implemented throughout the kingdom.

Vibrational Spectroscopy for the Triage of Traumatic Brain Injury Computed Tomography Priority and Hospital Admissions.

Computed tomography (CT) brain imaging is routinely used to support clinical decision-making in patients with traumatic brain injury (TBI). Only 7% of scans, however, demonstrate evidence of TBI. The other 93% of scans contribute a significant cost to the healthcare system and a radiation risk to patients. There may be better strategies to identify which patients, particularly those with mild TBI, are at risk of deterioration and require hospital admission. We introduce a blood serum liquid biopsy that utilizes attenuated total reflectance (ATR)-Fourier transform infrared (FTIR) spectroscopy with machine learning algorithms as a decision-making tool to identify which patients with mild TBI will most likely present with a positive CT scan. Serum samples were obtained from patients (n = 298) patients who had acquired a TBI and were enrolled in CENTER-TBI and from asymptomatic control patients (n = 87). Injury patients (all severities) were stratified against non-injury controls. The cohort with mild TBI was further examined by stratifying those who had at least one CT abnormality against those who had no CT abnormalities. The test performed exceptionally well in classifications of patients with mild injury versus non-injury controls (sensitivity = 96.4% and specificity = 98.0%) and also provided a sensitivity of 80.2% when stratifying mild patients with at least one CT abnormality against those without. The results provided illustrate the test ability to identify four of every five CT abnormalities and show great promise to be introduced as a triage tool for CT priority in patients with mild TBI.

FcγRIIIa receptor interacts with androgen receptor and PIP5K1α to promote growth and metastasis of prostate cancer.

Low-affinity immunoglobulin gamma Fc region receptor III-A (FcγRIIIa) is a cell surface protein that belongs to a family of Fc receptors that facilitate the protective function of the immune system against pathogens. However, the role of FcγRIIIa in prostate cancer (PCa) progression remained unknown. In this study, we found that FcγRIIIa expression was present in PCa cells and its level was significantly higher in metastatic lesions than in primary tumors from the PCa cohort (P = 0.006). PCa patients with an elevated level of FcγRIIIa expression had poorer biochemical recurrence (BCR)-free survival compared with those with lower FcγRIIIa expression, suggesting that FcγRIIIa is of clinical importance in PCa. We demonstrated that overexpression of FcγRIIIa increased the proliferative ability of PCa cell line C4-2 cells, which was accompanied by the upregulation of androgen receptor (AR) and phosphatidylinositol-4-phosphate 5-kinase alpha (PIP5Kα), which are the key players in controlling PCa progression. Conversely, targeted inhibition of FcγRIIIa via siRNA-mediated knockdown or using its inhibitory antibody suppressed growth of xenograft PC-3 and PC-3M prostate tumors and reduced distant metastasis in xenograft mouse models. We further showed that elevated expression of AR enhanced FcγRIIIa expression, whereas inhibition of AR activity using enzalutamide led to a significant downregulation of FcγRIIIa protein expression. Similarly, inhibition of PIP5K1α decreased FcγRIIIa expression in PCa cells. FcγRIIIa physically interacted with PIP5K1α and AR via formation of protein-protein complexes, suggesting that FcγRIIIa is functionally associated with AR and PIP5K1α in PCa cells. Our study identified FcγRIIIa as an important factor in promoting PCa growth and invasion. Further, the elevated activation of FcγRIII and AR and PIP5K1α pathways may cooperatively promote PCa growth and invasion. Thus, FcγRIIIa may serve as a potential new target for improved treatment of metastatic and castration-resistant PCa.

Assessment of biological risk among dentists during the COVID-19 Pandemic-A cross-sectional study.

Background: The health and life of a healthcare worker are repeatedly under threat due to the rising number of epidemics and pandemics. The COVID-19 pandemic is said to be fatal in people with a risky biological, demographic profile and working environment. This study is the first of its kind carried out on the dentist population from India, who were most affected during the COVID-19 pandemic. Aims and Objective: The present study aims to assess the biological risk of dentists based on the objective risk stratification (ORS) tool developed by Strain et al. Materials and Methods: This was a cross-sectional study of dentists in government dental colleges of Kerala using the online form of the ORS tool consisting of questions which included certain demographic characteristics and comorbid conditions of the individual. An additional question was added to the tool, to categorise the work of the dentist depending on the exposure to aerosol (non-aerosol, minimal aerosol and aerosol). Results: Out of the 74 dentists, 48.6% reported high aerosol and 31% with minimal aerosol. The median score of the study participants was 2 (ranging from 1 to 12). Using the ORS tool, 16.2% had medium risk and only 2.7% had high risk. When the ORS tool was stratified with the aerosol generation, 5.4% had minimal and 6.7% had significant with medium-risk scores. Also, 2.7% with a high-risk score had minimal aerosol generation. Conclusion: Identifying the high-risk category to allocate duties accordingly and decrease the morbidity and mortality among dentists has to be kept a top priority in the event of a pandemic.

Rapid Spectroscopic Liquid Biopsy for the Universal Detection of Brain Tumours.

BACKGROUND: To support the early detection and diagnosis of brain tumours we have developed a rapid, cost-effective and easy to use spectroscopic liquid biopsy based on the absorbance of infrared radiation. We have previously reported highly sensitive results of our approach which can discriminate patients with a recent brain tumour diagnosis and asymptomatic controls. Other liquid biopsy approaches (e.g., based on tumour genetic material) report a lower classification accuracy for early-stage tumours. In this manuscript we present an investigation into the link between brain tumour volume and liquid biopsy test performance. METHODS: In a cohort of 177 patients (90 patients with high-grade glioma (glioblastoma (GBM) or anaplastic astrocytoma), or low-grade glioma (astrocytoma, oligoastrocytoma and oligodendroglioma)) tumour volumes were calculated from magnetic resonance imaging (MRI) investigations and patients were split into two groups depending on MRI parameters (T1 with contrast enhancement or T2/FLAIR (fluid-attenuated inversion recovery)). Using attenuated total reflection (ATR)-Fourier transform infrared (FTIR) spectroscopy coupled with supervised learning methods and machine learning algorithms, 90 tumour patients were stratified against 87 control patients who displayed no symptomatic indications of cancer, and were classified as either glioma or non-glioma. RESULTS: Sensitivities, specificities and balanced accuracies were all greater than 88%, the area under the curve (AUC) was 0.98, and cancer patients with tumour volumes as small as 0.2 cm3 were correctly identified. CONCLUSIONS: Our spectroscopic liquid biopsy approach can identify gliomas that are both small and low-grade showing great promise for deployment of this technique for early detection and diagnosis.

Heterogeneity among enhancer RNAs: origins, consequences and perspectives.

Enhancer RNAs (eRNAs) are non-coding RNAs transcribed from distal cis-regulatory elements (i.e. enhancers), which are stereotyped as short, rarely spliced and unstable. In fact, a non-negligible fraction of eRNAs seems to be longer, spliced and more stable, and their cognate enhancers are epigenomically and functionally distinguishable from typical enhancers. In this review, we first summarized the genomic and molecular origins underlying the observed heterogeneity among eRNAs. Then, we discussed how their heterogeneous properties (e.g. stability) affect the modes of interaction with their regulatory partners, from promiscuous cis-interactions to specific trans-interactions. Finally, we highlighted the existence of a seemingly continuous spectrum of eRNA properties and its implications in the genomic origins of non-coding RNA genes from an evolutionary perspective.

Targeted inhibition of ERα signaling and PIP5K1α/Akt pathways in castration-resistant prostate cancer.

Selective ERα modulator, tamoxifen, is well tolerated in a heavily pretreated castration-resistant prostate cancer (PCa) patient cohort. However, its targeted gene network and whether expression of intratumor ERα due to androgen deprivation therapy (ADT) may play a role in PCa progression is unknown. In this study, we examined the inhibitory effect of tamoxifen on castration-resistant PCa in vitro and in vivo. We found that tamoxifen is a potent compound that induced a high degree of apoptosis and significantly suppressed growth of xenograft tumors in mice, at a degree comparable to ISA-2011B, an inhibitor of PIP5K1α that acts upstream of PI3K/AKT survival signaling pathway. Moreover, depletion of tumor-associated macrophages using clodronate in combination with tamoxifen increased inhibitory effect of tamoxifen on aggressive prostate tumors. We showed that both tamoxifen and ISA-2011B exert their on-target effects on prostate cancer cells by targeting cyclin D1 and PIP5K1α/AKT network and the interlinked estrogen signaling. Combination treatment using tamoxifen together with ISA-2011B resulted in tumor regression and had superior inhibitory effect compared with that of tamoxifen or ISA-2011B alone. We have identified sets of genes that are specifically targeted by tamoxifen, ISA-2011B or combination of both agents by RNA-seq. We discovered that alterations in unique gene signatures, in particular estrogen-related marker genes are associated with poor patient disease-free survival. We further showed that ERα interacted with PIP5K1α through formation of protein complexes in the nucleus, suggesting a functional link. Our finding is the first to suggest a new therapeutic potential to inhibit or utilize the mechanisms related to ERα, PIP5K1α/AKT network, and MMP9/VEGF signaling axis, providing a strategy to treat castration-resistant ER-positive subtype of prostate cancer tumors with metastatic potential.

Differentiating Nonenhancing Grade II Gliomas from Grade III Gliomas Using Diffusion Tensor Imaging and Dynamic Susceptibility Contrast MRI.

BACKGROUND: Contrast enhancement in a brain tumor on magnetic resonance imaging is typically indicative of a high-grade glioma. However, a significant proportion of nonenhancing gliomas can be either grade II or III. While gross total resection remains the primary goal, imaging biomarkers may guide management when surgery is not possible, especially for nonenhancing gliomas. The utility of diffusion tensor imaging and dynamic susceptibility contrast magnetic resonance imaging was evaluated in differentiating nonenhancing gliomas. METHODS: Retrospective analysis was performed on imaging data from 72 nonenhancing gliomas, including grade II (n = 49) and III (n = 23) gliomas. Diffusion tensor imaging and dynamic susceptibility contrast data were used to generate fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity as well as cerebral blood volume, cerebral blood flow, and mean transit time maps. Univariate and multivariate logistic regression and area under the curve analyses were used to measure sensitivity and specificity of imaging parameters. A subanalysis was performed to evaluate the utility of imaging parameters in differentiating between different histologic groups. RESULTS: Logistic regression analysis indicated that tumor volume and relative mean transit time could differentiate between grade II and III nonenhancing gliomas. At a cutoff value of 0.33, this combination provided an area under the curve of 0.71, 70.6% sensitivity, and 64.3% specificity. Logistic regression analyses demonstrated much higher sensitivity and specificity in the differentiation of astrocytomas from oligodendrogliomas or identification of grades within these histologic subtypes. CONCLUSIONS: Diffusion tensor imaging and dynamic susceptibility contrast imaging can aid in differentiation of nonenhancing grade II and III gliomas and between histologic subtypes.