In this report, we demonstrate that continuous improvement in XPS instruments and the calibration standards as well
as analysis with standard component-fitting procedures can be used to determine the binding energies of compounds
containing phosphorus and sulfur of different oxidation states with higher confidence. Based on such improved XPS
analyses, the binding energies (BEs) of S2p signals for sulfur of increasing oxidation state are determined to be 166-167.5
eV for S=O in dimethyl sulfoxide, 168.1 eV for S=O2
in polysulfone, 168.4 eV for SO3
in polystyrene sulfonate and 168.8
eV for SO4
in chondroitin sulfate. The BEs of P2p signals show the following values: 132.9 eV for PO3
in triisopropyl
phosphite, 133.3 eV for PO4
in glycerol phosphate, 133.5 eV for PO4
in sodium tripolyphosphate and 134.0 eV for PO4
in sodium hexametaphosphate. These results showed that there are only small increases in the binding energy when
additional oxygen atoms are added to the S-O chemical group. A similar result is obtained when the fourth oxygen or
poly-phosphate environment is added to the phosphorus compound. These BE values are useful to researchers involved
in identifying oxidation states of phosphorus and sulfur atoms commonly observed on modified surfaces and interfaces
found in applications such as biomaterials, super-capacitors and catalysis.
Influenza still remains one of the most challenging diseases, posing a significant threat to public health. Host lipid rafts play a critical role in influenza A virus (IAV) assembly and budding, however, their role in polyvalent IAV host binding and endocytosis had remained elusive until now. In the present study, we observed co-localization of IAV with a lipid raft marker ganglioside, GM1, on the host surface. Further, we isolated the lipid raft micro-domains from IAV infected cells and detected IAV protein in the raft fraction. Finally, raft disruption using Methyl-β-Cyclodextrin revealed significant reduction in IAV host binding, suggesting utilization of host rafts for polyvalent binding on the host cell surface. In addition to this, cyclodextrin mediated inhibition of raft-dependent endocytosis showed significantly reduced IAV internalization. Interestingly, exposure of cells to cyclodextrin two hours post-IAV binding showed no such reduction in IAV entry, indicating use of raft-dependent endocytosis for host entry. In summary, this study demonstrates that host lipid rafts are selected by IAV as a host attachment factors for multivalent binding, and IAV utilizes these micro-domains to exploit raft-dependent endocytosis for host internalization, a virus entry route previously unknown for IAV.
Lipid rafts are ubiquitous in cells. They are identified as cholesterol and glycosphingolipid enriched microdomains on cellular membranes. They serve as platforms for cellular communications by functioning in signal transduction and membrane trafficking. Such structural organisation fulfils cellular needs for normal function, but at the same time increases vulnerability of cells to pathogen invasion. Viruses rely heavily on lipid rafts in basically every stage of the viral life cycle for successful infection. Various mechanisms of lipid rafts modification exploited by diverse viruses for attachment, internalisation, membrane fusion, genome replication, assembly and release have been brought to light. This review focuses on virus-raft interactions and how a wide range of viruses manipulate lipid rafts at distinct stages of infection. The importance of virus-raft interactions in viral infections has inspired researchers to discover and develop antivirals that target this interaction, such as statins, methyl-β-cyclodextrin, viperin, 25-hydroxycholesterol and even anti-malarial drugs. The therapeutic modulations of lipid rafts as potential antiviral intervention from in vitro and in vivo evidence are discussed herein.
Three major outbreaks of the coronavirus, a zoonotic virus known to cause respiratory disease, have been reported since 2002, including SARS-CoV, MERS-CoV and the most recent 2019-nCoV, or more recently known as SARS-CoV-2. Bats are known to be the primary animal reservoir for coronaviruses. However, in the past few decades, the virus has been able to mutate and adapt to infect humans, resulting in an animal-to-human species barrier jump. The emergence of a novel coronavirus poses a serious global public health threat and possibly carries the potential of causing a major pandemic outbreak in the naïve human population. The recent outbreak of COVID-19, the disease caused by SARS-CoV-2, in Wuhan, Hubei Province, China has infected over 36.5 million individuals and claimed over one million lives worldwide, as of 8 October 2020. The novel virus is rapidly spreading across China and has been transmitted to 213 other countries/territories across the globe. Researchers have reported that the virus is constantly evolving and spreading through asymptomatic carriers, further suggesting a high global health threat. To this end, current up-to-date information on the coronavirus evolution and SARS-CoV-2 modes of transmission, detection techniques and current control and prevention strategies are summarized in this review.
Traditionally, drug discovery utilises a de novo design approach, which requires high cost and many years of drug development before it reaches the market. Novel drug development does not always account for orphan diseases, which have low demand and hence low-profit margins for drug developers. Recently, drug repositioning has gained recognition as an alternative approach that explores new avenues for pre-existing commercially approved or rejected drugs to treat diseases aside from the intended ones. Drug repositioning results in lower overall developmental expenses and risk assessments, as the efficacy and safety of the original drug have already been well accessed and approved by regulatory authorities. The greatest advantage of drug repositioning is that it breathes new life into the novel, rare, orphan, and resistant diseases, such as Cushing's syndrome, HIV infection, and pandemic outbreaks such as COVID-19. Repositioning existing drugs such as Hydroxychloroquine, Remdesivir, Ivermectin and Baricitinib shows good potential for COVID-19 treatment. This can crucially aid in resolving outbreaks in urgent times of need. This review discusses the past success in drug repositioning, the current technological advancement in the field, drug repositioning for personalised medicine and the ongoing research on newly emerging drugs under consideration for the COVID-19 treatment.
Dentin dysplasia is an exceptionally rare, autosomal-dominant, hereditary condition, primarily characterized by defective dentin formation affecting both the deciduous and permanent dentitions. The etiology remains imprecise to date, in spite of the numerous hypotheses put forward and the constant updates on this condition. This case report of type I dentin dysplasia exhibits radiographic findings that are unique and diverse from the classical findings of various subtypes of this disease reported to date. This article also depicts the implant-based oral rehabilitation of the young patient diagnosed with this variant model of dentin dysplasia type I. Early diagnosis and implementation of this preventive and curative therapy is vital for avoiding premature exfoliation of deciduous and permanent dentition and the associated residual ridge resorption, thereby overcoming functional and esthetic deficits and ensuring protection of the remaining dentition from further harm.
The case notes of twelve jaundiced patients, on whom percutaneous transhepatic cholangiography (PTC) were performed, are reviewed. PTC was carried out to differentiate the patients with intrahepatic cholestasis from those with extrahepatic biliary obstruction, and to identify the site and nature of the block. In eleven cases, the biliary trees were visualised, with the sites of obstruction in those present demonstrated and confirmed at subsequent laparotomies. There was no serious side effect from the procedure. PTC in our hands has proved an invaluable aid in the investigation of the icteric patients.
There are numerous pygmy grasshoppers (Tetrigidae) that exhibit leaf-like appearance. Leaf-mimic species can be found mainly in the subfamily Cladonotinae (tribes Cladonotini, Xerophyllini). Two leaf-mimic pygmy grasshopper species found in India, Pakistan (Oxyphyllum pennatum Hancock, 1909) and Borneo (Paraphyllum antennatum Hancock, 1913) are the only macropterous leaf-like species of Asia and were traditionally assigned to subfamily Cladonotinae. Our study present new records of these species, as well as updated descriptions. Oxyphyllum pennatum is recorded for the first time from Chhattisgarh (Central India), and furthermore, records from Pakistan were reviewed and confirmed. Paraphyllum antennatum is reported from a few localities in the mountains of Borneo (East Malaysia). New records found in online social media (Flickr, iNaturalist) were implemented. Brachypronotal specimens of P. antennatum are reported. After comparison with Cladonotini and Xerophyllini members, we conclude that Oxyphyllum and Paraphyllum should not be regarded Cladonotinae members. Traditional assignment was based on superficial resemblance to leaf-like Cladonotinae genera (e.g. Phyllotettix, Hymenotes, Holoarcus, Xerophyllum). However, comparison of morphological characters reveals that Oxyphyllum shares morphology with Tetriginae genera, while Paraphyllum shares morphology with Asian Metrodorinae. Here, we assign the genus Oxyphyllum to Tetriginae and the genus Paraphyllum to Metrodorinae.
Introduction: With introduction of the term "ossteointegration of dental implant" by Branemark, advancement in implantology from 1957 to 2017 has come a long way with modification in implant type and in loading time. This study aims to evaluate the survival of endo-osseous immediate loading (IL) implant and basal IL implants in atrophic jaws with objective to compare implant survival in atrophic jaws for full mouth rehabilitation between endo-osseous IL versus endo-osseous delayed loading (DL) versus basal IL during 3-year follow-up.
Materials and Methods: Fifty-two (34 endo-osseous and 18 basal) implants were placed in 4 patients requiring full mouth rehabilitation in atrophic jaws. Case 1: Endo-osseous DL implants in upper and lower arch, Case 2: Endo-osseous IL implants in upper and lower arch, Case 3: Basal IL implant in upper and lower arch, and Case 4: Endo-osseous DL in upper arch and basal IL implant in the lower arch. Intraoperative evaluation was done on the basis of pain (visual analog scale [VAS]), operative time, and initial primary implant stability. Postoperative evaluation was done on pain (VAS), infection, radiographically successful implant (orthopantomogram), and patient satisfaction (Grade 0-10).
Results: All cases showed satisfactory results but more amount of intra- and post-operative pain was felt with immediate basal implants.
Conclusion: We believe that clinicians should comply with patient requests, and for this reason, we agree with some authors to use minimally invasive techniques and to avoid when possible esthetic or functional problems associated with the use of removable prosthesis after teeth extractions.
Cannabis is a plant notorious for its psychoactive effect, but when used correctly, it provides a plethora of medicinal benefits. With more than 400 active compounds that have therapeutic properties, cannabis has been accepted widely as a medical treatment and for recreational purposes in several countries. The compounds exhibit various clinical benefits, which include, but are not limited to, anticancer, antimicrobial, and antioxidant properties. Among the vast range of compounds, multiple research papers have shown that cannabinoids, such as cannabidiol and delta-9-tetrahydrocannabinol, have antiviral effects. Recently, scientists found that both compounds can reduce severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) viral infection by downregulating ACE2 transcript levels and by exerting anti-inflammatory properties. These compounds also act as the SARS-CoV-2 main protease inhibitors that block viral replication. Apart from cannabinoids, terpenes in cannabis plants have also been widely explored for their antiviral properties. With particular emphasis on four different viruses, SARS-CoV-2, human immunodeficiency virus, hepatitis C virus, and herpes simplex virus-1, this review discussed the role of cannabis compounds in combating viral infections and the potential of both cannabinoids and terpenes as novel antiviral therapeutics.
In the present study, a simple and sensitive method for detecting bisphenol A (BPA) in various environments, including groundwater, was described using a widespread electrochemical method. BPA is well-known for its endocrine-disrupting properties, which may cause potential toxicological effects oon the nervous, reproductive, and immune systems. A novel metal-organic framework (UiO-66-NDC/GO) was synthesized, and its existence was confirmed by several characterization techniques like FTIR, UV-visible, XRD, SEM-EDX, Raman spectroscopy, and TGA. Due to the excellent electrocatalytic nature, UiO-66-NDC/GO was chosen as the sensor material and integrated on the surface of the bare carbon paste electrode (BCPE). The UiO-66-NDC/GO modified carbon paste electrode (MCPE) was engaged for the detection of BPA using techniques like cyclic Voltammetry (CV), differential pulse voltammetry (DPV), and electrochemical impedance spectroscopy (EIS). The applied sensor exhibited an astonishing outcome for BPA detection with high sensitivity and selectivity. The lower detection limit (LLOD) of 0.025 μM was achieved at the modified sensor with a linear concentration range of 10-70 μM. Moreover, the practical applicability of the sensor was tested on tap water, drinking water, and fresh liquid milk, giving an excellent recovery of BPA in the range of 94.8-99.3 (v.%). The proposed method could be employed for electrochemical device or a solid state device fabrication for the onsite monitoring of BPA.
There is need to confirm the presence of Theileria orientalis among the cattle population in Peninsular Malaysia and to evaluate the risk factors associated with the infection. To this effect, blood samples were collected from 1045 cattle from 43 farms throughout the entire States of Peninsular Malaysia. The collected blood samples were subjected to DNA extraction and subsequent PCR amplification of the major piroplasm surface protein (MPSP) gene of the haemoprotozoan. Representative positive amplicons were purified, sequenced and compared with other sequences of the MPSP gene of T. orientalis curated from the GenBank. A well-structured questionnaire was used to get information about each cattle, it's demography, the bio-security, environmental and management factors. Univariate and multivariate analysis were used for the statistical evaluation, with significance set at p < 0.05. A total prevalence of 49.76% (520/1045; 95% CI: 46.73 - 52.79) was obtained. Types of breeds, age, production type, herd size, level of farm biosecurity, farm size, presence of other animal species in the farm, management systems and prophylaxis were significantly (p < 0.05) associated with the prevalence of T. orientalis. This study confirmed the presence of T. orientalis and establish that the haemoprotozoan is endemic among cattle in Peninsular Malaysia.
The incidences of fungal infections have greatly increased over the past few years, particularly in humid and industrialized areas. The severity of such infections ranges from being asymptomatic-mild to potentially life-threatening systemic infections. There are limited classes of drugs that are approved for the treatment of such infections like polyenes, azoles, and echinocandins. Some fungi have developed resistance to these drugs. Therefore, to counter drug resistance, intensive large scale studies on novel targeting strategies and formulations are being conducted, which have gained impetus lately. Conventional formulations have limitations such as higher doses, frequent dosing, and several side effects. Such limiting factors have paved the path for the emergence of nanotechnology and its applications. This further gave formulation scientists the possibility of encapsulating the existing potential drug moieties into nanocarriers, which when loaded into gels or creams provided prolonged release and improved permeation, thus giving on-target effect. This review thus discusses the newer targeting strategies and the role of nanocarriers that could be administered topically for the treatment of various fungal infections. Furthermore, this approach opens newer avenues for continued and sustained research in pharmaceuticals with much more effective outcomes.
Peptides and proteins have emerged as potential therapeutic agents and, in the search for the best treatment regimen, the oral route has been extensively evaluated because of its non-invasive and safe nature. The physicochemical properties of peptides and proteins along with the hurdles in the gastrointestinal tract (GIT), such as degrading enzymes and permeation barriers, are challenges to their delivery. To address these challenges, several conventional and novel approaches, such as nanocarriers, site-specific and stimuli specific delivery, are being used. In this review, we discuss the challenges to the oral delivery of peptides and the approaches used to tackle these challenges.
Babesia bigemina is a tick-borne protozoan that affects cattle in almost all regions of the world. Despite its importance, there is no report of its prevalence in cattle using molecular detection methods in Peninsular Malaysia. This study describes the prevalence, distribution, and risk factors associated with B. bigemina infection using molecular diagnostic methods. Also, the species of ticks infesting cattle and the attitude of cattle farmers towards tick control in Peninsular Malaysia were studied. Blood samples were collected from 1045 cattle from 43 herds throughout the country, and were subjected to molecular studies to detect B. bigemina. Tick samples for entomological studies were also collected and identified. Epidemiological information of each cattle and farm were obtained using a well-structured questionnaire containing open-ended and closed-ended questions. Data were statistically analyzed using Univariate and Multivariate models. The 211-base pair of AMA-1 gene of B. bigemina was amplified and confirmed in 30.5 % (319/1045; 95 % CI = 27.8-33.4) of the sampled population, with the haemoprotozoan detected in all the sampled herds. Breed, age, physiological status, management type, rate of de-ticking, and closeness to human settlement were the risk factors significantly (p < 0.05) associated with the prevalence of B. bigemina in cattle. Rhipicephalus (Boophilus) microplus and Haemaphysalis bispinosa were the species of ticks collected from cattle, with the former been more prevalent. A large number of cattle farmers (12/43; 28 %) do not control ticks in their herds. The findings of this study will create baseline data on the epidemiology of the haemoprotozoan and control patterns of its tick vectors that will guide the government in enacting policies that will improve food security and the economy of the nation.
Introduction: Vaccine development for the disease caused by the herpes simplex virus (HSV) has been challenging over the years and is always in dire need of novel approaches for prevention and cure. To date, the HSV disease remains incurable and challenging to prevent. The disease is extremely widespread due to its high infection rate, resulting in millions of infection cases worldwide.Areas covered: This review first explains the diverse forms of HSV-related disease presentations and reports past vaccine history for the disease. Next, this review examines current and novel HSV vaccine approaches being studied and tested for efficacy and safety as well as vaccines in clinical trial phases I to III. Modern approaches to vaccine design using bioinformatics are described. Finally, we discuss measures to enhance new vaccine development pipelines for HSV.Expert opinion: Modernized approaches using in silico analysis and bioinformatics are emerging methods that exhibit potential for producing vaccines with enhanced targets and formulations. Although not yet fully established for HSV disease, we describe current studies using these approaches for HSV vaccine design to shed light on these methods. In addition, we provide up-to-date requirements of immunogenicity, adjuvant selection, and routes of administration.
A tumor serves as a major avenue in drug development owing to its complexity. Conventional therapies against tumors possess limitations such as suboptimal therapeutic efficacy and extreme side effects. These display poor pharmacokinetics and lack specific targeting, with non-specific distribution resulting in systemic toxicity. Therefore, nanocarriers targeted against cancers are increasingly being explored. Nanomedicine aids in maintaining a balance between efficacy and toxicity by specifically accumulating in tumors. Nanotherapeutics possess advantages such as increased solubility of chemotherapeutics, encapsulation of multiple drugs and improved biodistribution, and can ensure tumor-directed drug delivery and release via the approaches of passive targeting and active targeting. This review aims to offer a general overview of the current advances in tumor-targeting nanocarriers for clinical and diagnostic use.
Psoriasis is a chronic autoimmune skin disorder affecting 2-3% of the world population. It has characteristic features such as increased keratinocyte proliferation and production of inflammatory mediators. The treatment involves various strategies including topical, systemic, phototherapy and biologics. Topical therapies are preferred for mild to moderate psoriasis conditions over the systemic therapies which are ideal in severe disease conditions. The systemic therapies include immunosuppressants, biological agents and recently approved phosphodiesterase-4 (PDE4) inhibitors. There are various limitations associated with the existing therapies where the new findings in the pathogenesis of psoriasis are paving a path for newer therapeutics to target at the molecular level. Various small molecules, PDE-4 inhibitors, biologics, and immunomodulator proved efficacious including the new molecules targeting Janus kinases (JAK) inhibitors that are under investigation. Furthermore, the role of genetic and miRNAs in psoriasis is still not completely explored and may further help in improving the treatment efficacy. This review provides an insight into various emerging therapies along with currently approved treatments for psoriasis.
Bovine anaplasmosis is a major concern to cattle farming in most parts of the world. Anaplasmosis negatively impacts the profitability of cattle farming by reducing the production, reproduction, and draft ability of cattle. Here, we report results from a one-year cross sectional study to determine the epidemiology and the risk factors for Anaplasma marginale infection of cattle in Peninsular Malaysia. Examination of one thousand and forty five blood samples of apparently healthy cattle from forty-three farms in all the states of Peninsular Malaysia by polymerase chain reaction (PCR) assay revealed an overall prevalence of A. marginale infection of cattle of 72.6%, showing high endemicity of this heamoprotozoan among cattle in the country. Cattle breeds, production type, herd owner, herd size, management system, farm size, farm age, prophylactic treatment against blood parasites, presence of ticks, frequency of deticking, zones, closeness to forest, closeness to waste area, closeness to human settlement and closeness to body of water were the risk factors significantly associated (P
Background: Periodontitis is a public health concern since it is a major factor in tooth loss worldwide and has association with many systemic diseases. Sleep is a complex and essentially biological process and a critical factor for maintaining mental and physical health. Since inflammation is characteristic of both chronic periodontitis and sleep deprivation, few studies in recent years present the contradictory results regarding this potential association. The objective of the present study was to investigate the association between quality of sleep and chronic periodontitis.
Materials and Methods: A total of 200 individuals participated in this study. All participants underwent a comprehensive clinical periodontal examination. Case-control were identified using the Centers for Disease Control and Prevention/American Academy of Periodontology case definitions for periodontal disease. The quality of sleep was assessed by Pittsburgh Sleep Quality Index. The univariate and multivariate logistic regression analysis was used to test the influence of variables (quality of sleep, age, sex, ethnicity, education, and socioeconomic status), in the occurrence of periodontitis. Odds ratio (OR) and respective confidence intervals (CIs) were calculated and reported. P =0.05 was considered statistically significant.
Results: The prevalence of poor quality of sleep was 56.75% in cases (periodontitis group) and 43.24% in control group. There was positive association between quality of sleep and chronic periodontitis (OR = 3.04; 95% CI = 1.42-6.5; P = 0.004). In multivariate logistic regression analysis, only the age was significantly related to the periodontitis (OR = 1.11; 95% CI = 1.07-1.41; P < 0.001), other variables failed to reach the significant level.
Conclusion: Poor quality of sleep was significantly associated with chronic periodontitis. Only the age was significantly related to periodontitis among the other covariable measured.