Association and expression of the antigen-processing gene PSMB8, coding for low-molecular-mass protease 7, with vitiligo in North India: case-control study.

BACKGROUND: Vitiligo is a multifactorial, autoimmune, depigmenting disorder of the skin where aberrant presentation of autoantigens may have a role. OBJECTIVES: To study the association of two antigen-processing genes, PSMB8 and PSMB9, with vitiligo. METHODS: In total 1320 cases of vitiligo (1050 generalized and 270 localized) and 752 healthy controls were studied for the PSMB9 exon 3 G/A single-nucleotide polymorphism (SNP), PSMB8 exon 2 C/A SNP and PSMB8 intron 6 G/T SNP at site 37 360 using polymerase chain reaction (PCR)-restriction fragment length polymorphism. Real-time PCR was used for transcriptional expression of PSMB8 and cytokines. Expression of ubiquitinated proteins and phosphorylated-p38 (P-p38) was studied by Western blotting. RESULTS: Significant increases in PSMB8 exon 2 allele A (P < 2.07 × 10-6 , odds ratio 1·93) and genotypes AA (P < 1.03 × 10-6 , odds ratio 2·51) and AC (P < 1.29 × 10-6 , odds ratio 1·63) were observed in patients with vitiligo. Interferon-γ stimulation induced lower expression of PSMB8 in peripheral blood mononuclear cells of cases compared with controls, suggesting impaired antigen processing, which was confirmed by accumulation of ubiquitinated proteins in both lesional and nonlesional skin of patients with vitiligo. Expression of proinflammatory cytokines - interleukin (IL)-6, IL-1ß and IL-8 - was higher in the lesional skin. P-p38 expression was variable but correlated with the amount of ubiquitinated proteins in the lesional and nonlesional skin, suggesting that the inflammatory cytokine responses in lesional skin could be a result of both P-p38-dependent and -independent pathways. CONCLUSIONS: The PSMB8 exon 2 SNP is significantly associated with vitiligo. Accumulation of ubiquitinated proteins in skin of cases of vitiligo suggests their aberrant processing, which may promote the development of the disease.

CHronic Rhinosinusitis Outcome MEasures (CHROME), developing a core outcome set for trials of interventions in chronic rhinosinusitis.

STATEMENT OF PROBLEM: Evaluating the effectiveness of treatments in chronic rhinosinusitis (CRS) have been limited by both a paucity of high quality randomised trials, and the heterogeneity of outcomes in those that have been reported. Core outcome sets (COS) are an agreed, standardized set of outcomes that should be measured and reported by future trials as a minimum and will facilitate future meta-analysis of trial results in systematic reviews (SRs). We set out to develop a core outcome set for interventions for adults with CRS. METHOD(S) OF STUDY: A long-list of potential outcomes was identified by a steering group utilising a literature review, thematic analysis of a wide range of stakeholders' views and systematic analysis of currently available Patient Reported Outcome Measures (PROMs). A subsequent e-Delphi process allowed 110 patients and healthcare practitioners to individually rate the outcomes in terms of importance, on a Likert scale. MAIN RESULTS: After 2 rounds of the iterative Delphi process, the 54 initial outcomes were distilled down to a final core-outcome set of 15 items, over 4 domains. PRINCIPAL CONCLUSIONS: The authors hope inclusion of these core outcomes in future trials will increase the value of research on interventions for CRS in adults. It was felt important to make recommendations regarding how these outcomes should be measured, although additional work is now required to further develop and revalidate existing outcome measures.

Evaluation of Surface Roughness of Nanofilled Composite Restorations after Simulated Tooth Brushing using Various Dentifrices.

Background Teeth restored with direct composite resin are constantly exposed to specific challenges of the oral cavity. These challenges can modify the material properties and, when associated with daily brushing, eventually change its surface roughness, allowing bacterial growth and retention of extrinsic pigments. Dentifrices plays an important role in dental wear (abrasion) and over time, can also cause an increase in the surface roughness of restorative materials. Objective To assess the effect of dentifrices on the longevity of direct nanofilled composite resins restorations as far as wear and roughness is concerned. Method Class V cavity were prepared on 90 extracted human teeth and restored with Filtek Z350 composite. Teeth were randomly divided into 6 experimental groups of 15 each labelled as Group-1 (Colgate Dental cream) Group-2 (Colgate Active Salt toothpaste), Group-3 (Pepsodent Regular toothpaste), Group-4 (Dabur red toothpaste), Group-5 (Dabur Lal tooth powder) and Group-6 Control (water). The samples were fixed on tooth brushing machine and subjected to mechanical tooth brushing using various dentifrices according to respective groups in 3 phases and reading of surface roughness (Ra) was recorded. Result Surface roughness (Ra) had increased in following order: Group 6 < Group 3 < Group 2 < Group 1 < Group 4 < Group 5. All the tooth pastes were compared, their behaviour was found to be similar as there was no statistically significant difference amongst them. Though all of them were inferior to control group and the difference was statistically significant. Whereas the only tooth powder Dabur lal tooth powder gave the maximum roughness when compared with the other tooth pastes and the difference was statistically significant. Conclusion With increase in time of brushing there was increase in surface roughness in all the 5 dentifrices among them Ra was maximum for Dabur lal tooth powder.

Immunoprotective responses of T helper type 1 stimulatory protein-S-adenosyl-L-homocysteine hydrolase against experimental visceral leishmaniasis.

It is well known that a patient in clinical remission of visceral leishmaniasis (VL) remains immune to reinfection, which provides a rationale for the feasibility of a vaccine against this deadly disease. In earlier studies, observation of significant cellular responses in treated Leishmania patients as well as in hamsters against leishmanial antigens from different fractions led to its further proteomic characterization, wherein S-adenosyl-L-homocysteine hydrolase (AdoHcy) was identified as a helper type 1 (Th1) stimulatory protein. The present study includes immunological characterization of this protein, its cellular responses [lymphoproliferation, nitric oxide (NO) production and cytokine responses] in treated Leishmania-infected hamsters and patients as well as prophylactic efficacy against Leishmania challenge in hamsters and the immune responses generated thereof. Significantly higher cellular responses were noticed against recombinant L. donovani S-adenosyl-L-homocysteine hydrolase (rLdAdoHcy) compared to soluble L. donovani antigen in treated samples. Moreover, stimulation of peripheral blood mononuclear cells with rLdAdoHcy up-regulated the levels of interferon (IFN)-γ, interleukin (IL)-12 and down-regulated IL-10. Furthermore, vaccination with rLdAdoHcy generated perceptible delayed-type hypersensitivity response and exerted considerably good prophylactic efficacy (∼70% inhibition) against L. donovani challenge. The efficacy was confirmed by the increased expression levels of inducible NO synthase and Th1-type cytokines, IFN-γ and IL-12 and down-regulation of IL-4, IL-10 and transforming growth factor (TGF)-ß. The results indicate the potentiality of rLdAdoHcy protein as a suitable vaccine candidate against VL.

A unique case of rituximab-related posterior reversible encephalopathy syndrome in a heart transplant recipient with posttransplant lymphoproliferative disorder.

Rituximab is commonly used as a first line therapy to treat posttransplant lymphoproliferative disorders (PTLDs). It has also proved useful in the management of refractory antibody mediated graft rejection. We report an unusual case in which a heart transplant recipient being treated with rituximab for PTLD developed altered mental status, hallucinations and visual symptoms and magnetic resonance imaging (MRI) findings of symmetrical enhancement suggestive of posterior reversible leukoencephalopathy syndrome (PRES). Resolution of these clinical symptoms and radiological findings after discontinuation of therapy confirmed the diagnosis. This is the first case of PRES seen due to rituximab in a heart transplant recipient. Another unique feature of the case is the development of PRES after second cycle of rituximab as compared to prior reports in nonheart transplant patients in which the syndrome developed after first dose administration. The objective of this case report is to increase the awareness of this rare entity amongst immunocompromised transplant patients.

The impact of commissioning for rhinosinusitis in England.

OBJECTIVES: To assess the compliance of clinical commissioning groups (CCGs) in England with the ENT-UK rhinosinusitis commissioning guide produced in collaboration with the Royal College of Surgeons England and the National Institute of Clinical Excellence. We also aimed to assess the ease of accessibility of data from CCGs. DESIGN: Audit of compliance of English CCGs with the ENT-UK rhinosinusitis commissioning guide. SETTING: CCGs in England PARTICIPANTS: A total of 58 of the 221 CCGs in England were included and chosen because they were the first CCGs authorised by NHS England, or alternately, the CCGs forecasted to have a deficit in their first year of operation. Their websites were reviewed; when information was not easily accessible, a freedom of information request was submitted to the relevant CCG. MAIN OUTCOME MEASURES: Compliance with commissioning guidelines for rhinosinusitis. RESULTS: Thirteen percent of CCGs had restrictive referral criteria in place, largely unrelated to published evidence-based guidance. The routine use of multiple courses of oral steroids, prescription of antibiotics, CT scanning within primary care, and delaying referral for a year, prior to referral to a specialist were recommended against published advice. CONCLUSIONS: Restricting access to surgery may contribute to poorer outcomes and a decrease in the patient's quality of life. This is against the NHS constitution and is open to legal challenge. We encourage all ENT surgeons to review policies of their local CCG and engage with commissioners to ensure that their patients have evidence-based care.

miRNA-transcription factor interactions: a combinatorial regulation of gene expression.

Developmental processes require a precise spatio-temporal regulation of gene expression wherein a diverse set of transcription factors control the signalling pathways. MicroRNAs (miRNAs), a class of small non-coding RNA molecules have recently drawn attention for their prominent role in development and disease. These tiny sequences are essential for regulation of processes, including cell signalling, cell development, cell death, cell proliferation, patterning and differentiation. The consequence of gene regulation by miRNAs is similar to that by transcription factors (TFs). A regulatory cascade essential for appropriate execution of several biological events is triggered through a combinatorial action of miRNAs and TFs. These two important regulators share similar regulatory logics and bring about a cooperative action in the gene regulatory network, dependent on the binding sites present on the target gene. The review addresses the biogenesis and nomenclature of miRNAs, outlines the mechanism of action and regulation of their expression, and focuses on the combinatorial action of miRNAs and TFs for the expression of genes in various regulatory cascades.

Cloning and characterization of cold, salt and drought inducible C-repeat binding factor gene from a highly cold adapted ecotype of Lepidium latifolium L.

The dehydration-responsive element-binding (DREB) protein/C-Repeat Binding Factors (CBFs) belongs to APETALA2 (AP2) family transcription factors that binds to DRE/CRT cis-element in cold-responsive (COR) genes and induce COR genes. CBFs have been isolated and characterized from evolutionarily diverse plant species. CBF pathway is conserved by CBF regulon and the size or the number and kind of target genes vary among freezing sensitive and tolerant plants. Hence, cloning of CBFs from highly freezing tolerant plants such as Lepidium latifolium L. will be useful in understanding the freezing tolerance of this species. In this study, LlCBF, a CBF1 family gene from L. Latifolium L., was cloned using RT-PCR and RACE-PCR. The full length mRNA of LlCBF is 948 bp with an open reading frame of 642 bp, encoding a protein of 213 amino acids with a molecular weight of 23.92 kDa and a theoretical isoelectric point of 4.80. Amino acid sequence analysis showed that LlCBF has an AP2 DNA binding domain, a potential CBF type nuclear localization signal (NLS) and C-terminal acidic domain. Semi-quantitative RT-PCR analysis of LlCBF revealed that this gene is up-regulated by high salt, dehydration and low temperature stresses. The investigation is therefore successful in cloning of a gene having strong homology with CBF transcription factors and responsive to low temperature, high salt and dehydration conditions.

Effect of surgical intervention on serum insulin-like growth factor 1 in patients with obstructive sleep apnoea.

OBJECTIVE: To evaluate the effect of surgical intervention on serum insulin-like growth factor 1 levels in patients with obstructive sleep apnoea. METHODS: A prospective study was conducted in a tertiary care hospital of adult patients with obstructive sleep apnoea for whom continuous positive airway pressure therapy failed or was refused. All patients underwent polysomnography and serum insulin-like growth factor 1 evaluation pre-operatively and at three months post-operatively. The site of surgery was determined using Müller's manoeuvre and ApneaGraph AG 200. RESULTS: Fifteen patients were included with a mean age of 38 years: 11 males and 4 females. The mean pre-operative Apnoea-Hypopnoea Index using polysomnography was 53.7 events per hour, and the mean post-operative Apnoea-Hypopnoea Index at three months was 15.3 events per hour (p = 0.0001). The mean pre-operative serum insulin-like growth factor 1 was 160.2 µg/l, while the mean post-operative value was 236.98 µg/l (p = 0.005). CONCLUSION: In adult patients with obstructive sleep apnoea for whom continuous positive airway pressure therapy fails, site-specific surgical intervention to treat the obstruction leads to an increase in serum insulin-like growth factor 1 levels.

Linezolid: an effective, safe and cheap drug for patients failing multidrug-resistant tuberculosis treatment in India.

Linezolid is identified as an effective drug with which to treat patients failing multidrug-resistant (MDR)-tuberculosis (TB) treatment. However, cost and safety are the concerns. In India, the average price of a 600-mg pill of linezolid is less than one US dollar, much cheaper than most of the third-line drugs. A prospective study of 29 MDR-TB treatment failure patients (16 with laboratory-proven extensively drug-resistant (XDR)-TB and the remaining 13 with MDR-TB with resistance to any quinolone but sensitive to injectables) was carried out in Delhi, India. All patients received daily unsupervised therapy with linezolid, one injectable agent, one fluoroquinolone and two or more other drugs. Patients received a median of six anti-mycobacterial agents. Besides linezolid, capreomycin, moxifloxacin, levofloxacin and amoxycillin-clavulanic acid were used in 41.4%, 58.6%, 41.4%, and 79.3% of patients. Out of a total of 29 patients, 89.7% patients achieved sputum smear and culture conversion; 72.4% showed interim favourable outcome; 10.3% died, 6.8% failed and 10.3% patients defaulted. Linezolid had to be stopped in three (10.3%) patients due to adverse reactions. The outcome of treatment of 16 XDR-TB patients was comparable to the other 13 MDR-TB patients. Linezolid is an effective, cheap and relatively safe drug for patients failing MDR-TB treatment, including those with confirmed XDR-TB.

Facial neuritis in coronavirus disease 2019 associated mucormycosis: study on clinico-radiological correlates.

OBJECTIVE: To elucidate the aetiopathogenesis of facial neuritis in coronavirus disease 2019 associated mucormycosis. METHODS: A retrospective review was conducted of coronavirus disease 2019 associated mucormycosis patients who presented with peripheral facial nerve palsy from January 2021 to July 2021. The clinico-radiological details of four patients were assessed to examine the potential mechanism of facial nerve involvement. RESULTS: Serial radiological evaluation with contrast-enhanced computed tomography and contrast-enhanced magnetic resonance imaging revealed infratemporal fossa involvement in all cases, with the inflammation extending along fascial planes to reach the stylomastoid foramen. Ascending neuritis with an enhancement of the facial nerve was demonstrated in all cases. CONCLUSION: The likely explanation for facial palsy in patients with coronavirus disease 2019 associated mucormycosis, backed by radiology, is the disease abutting the facial nerve at the stylomastoid foramen and causing ascending neuritis of the facial nerve.

Adaptation of the gut pathobiont Enterococcus faecalis to deoxycholate and taurocholate bile acids.

Enterococcus faecalis is a natural inhabitant of the human gastrointestinal tract. This bacterial species is subdominant in a healthy physiological state of the gut microbiota (eubiosis) in adults, but can become dominant and cause infections when the intestinal homeostasis is disrupted (dysbiosis). The relatively high concentrations of bile acids deoxycholate (DCA) and taurocholate (TCA) hallmark eubiosis and dysbiosis, respectively. This study aimed to better understand how E. faecalis adapts to DCA and TCA. We showed that DCA impairs E. faecalis growth and possibly imposes a continuous adjustment in the expression of many essential genes, including a majority of ribosomal proteins. This may account for slow growth and low levels of E. faecalis in the gut. In contrast, TCA had no detectable growth effect. The evolving transcriptome upon TCA adaptation showed the early activation of an oligopeptide permease system (opp2) followed by the adjustment of amino acid and nucleotide metabolisms. We provide evidence that TCA favors the exploitation of oligopeptide resources to fuel amino acid needs in limiting oligopeptide conditions. Altogether, our data suggest that the combined effects of decreased DCA and increased TCA concentrations can contribute to the rise of E. faecalis population during dysbiosis.

Application of Baranyi function to model the antibacterial properties of solvent extract from Irish York cabbage against food spoilage and pathogenic bacteria.

Cabbage is a rich source of a number of bioactive compounds such as flavonoids, glucosinolates and their breakdown products which may have antibacterial, antioxidant and anticancer properties. Outer green leaves of York cabbage were extracted with 60% methanol, ethanol or acetone. Antibacterial activities of vacuum dried crude extracts were estimated against a number of Gram-positive and Gram-negative food spoilage and food pathogenic bacteria. The crude extracts showed a broad spectrum of antibacterial activities but 60% methanol extract exhibited the highest antibacterial effect. Complete growth inhibition for Listeria monocytogenes was achieved with an extract concentration of 1.4%, whereas a two-fold concentration was required to achieve a reduction of 75% and 64% for Salmonella abony and Pseudomonas aeruginosa, respectively. For Enterococcus faecalis methanolic extract showed a weak inhibition only (31%). The lower concentrations of methanolic extract from York cabbage prolonged the lag phase and reduced both the exponential growth rate and final population densities of the culture. Survival of the micro-organisms in presence of methanolic extract was mathematically modeled using Baranyi model equations.

A case of leprosy with multiple cranial neuropathy mimicking Melkerson Rosenthal syndrome.

Involvement of cranial nerves is not uncommon in leprosy with trigeminal and facial nerves being commonly affected. Other cranial nerves can also be involved especially in longstanding cases of leprosy towards the lepromatous pole. Herein, we report a case of leprosy with multiple cranial neuropathy mimicking Melkerson Rosenthal syndrome.

Glioblastoma with melanotic differentiation.

A 54-year-old male presented with the history of headache and vomiting. MRI of the head showed right posterior temporal mass which was surgically excised. Histopathological examination revealed features of glioblastoma with pigmented cells. The pigment was demonstrated to be melanin which was confirmed by special stains and immunohistochemistry. This is the first description of glioblastoma with melanotic differentiation reported in the literature. The relevant literature is briefly reviewed.

Bilateral lagophthalmos in leprosy: is it a rare phenomenon?

Lagophthalmos is one of the well known complications of leprosy due to involvement of the facial nerve. Herein, we report three cases of bilateral lagophthalmos due to leprosy which presented to us within a span of just three months. In all these cases, lagophthalmos was not the presenting complaint and it was detected by the treating doctor during examination. This report is being presented to highlight the importance of cranial nerve examination in all cases of leprosy as at times early changes of lagophthalmos may go unnoticed by the patient.

Prevalence of pharmacotherapy in the department of paediatric dentistry.

BACKGROUND: Pharmacotherapy plays important role in the management of paediatric dental patients in the department of paediatric dentistry. Many children at their early age suffer from different kinds of dental conditions such as acute and chronic irreversible pulpitis, acute and chronic alveolar abscesses, dentoalveolar and vestibular abscesses, etc along with physiological tooth movement that requires professional help for dental treatment. Treatment of such conditions most frequently requires pharmacotherapy as an either adjunct to dental therapeutic procedure or as a monotherapy. OBJECTIVE: To assess the prescribing patterns vis-a-vis generic or trade name, generic class, dosage form, route, frequency, duration, number of drugs per patient, cost and indication of drug therapy, patterns of dental treatment and Frankl's behavioral rating. MATERIALS AND METHODS: Prescriptions of 200 paediatric dental patients undergoing dental treatment in the department of paediatric dentistry were analyzed prospectively for a period of six months in a dental teaching hospital. RESULTS: 133 (56.5%) patients were males and 87 (43.5%) females and age group 6-10 years was the most frequent group (70%, P = 0.0000000) and all the patients received pharmacotherapy. Total numbers of 357 drugs were prescribed. Out of them, 212 (59.4%, P = 0.0000008) were analgesic agents, 133 (37.3%) antimicrobial agents (AMAs) and 12 (3.3%) other drugs. Extended spectrum Penicillins were the most commonly prescribed (90.2%) AMA followed by Metronidazole (9.8%). 247 drugs (69.2%, P = 0.0000000) were prescribed by trade names. 60% (P = 0.0000002) drugs were prescribed in the form of tablet or capsule followed by syrup 37% and administered entirely through oral route. Percentage of patients receiving three drugs, two drugs and one drug was 13.5%, 56.5% (P = 0.0000000) and 30% respectively and one patient received on average 1.78 medicines. 133 patients (56.5%, P = 0.0000000) received both AMA and analgesic agent. Minimum to maximum number of days for pharmacotherapy were 2 to 15 and highest frequency was up to four times a day. Cost of medicines was in the range of 10-150 Nepalese Rupees. Chronic irreversible pulpitis was the commonest diagnosis (28%) and extraction (92.5%) was the commonest dental procedure. Frankl's behaviour rating showed that 78.5% (P = 0.0000000) patients had positive attitude towards the dental procedures. CONCLUSION: Findings of the study suggest that pharmacotherapy is the mainstay in therapy to treat the paediatric dental patients along with dental procedures either to control the dental pain or odontogenic infection. Age group 6-10 years, chronic irreversible pulpitis and dental extraction are the commonest age group, diagnosis and dental procedure respectively in the department of paediatric dentistry. Analgesic (non-steroidal anti-inflammatory drugs- Nimesulide, Ibuprofen and Paracetamol) and Amoxicillin are the most frequently prescribed drugs mostly in the solid dosage forms in trade names via oral route. Duration of pharmacotherapy ranges from 2 to 15 days with highest frequency being up to 4 times a day. Majority of the patients are manageable without any behavioural modification technique- physical or pharmacological.

Anomalous pressure dependence of the electronic transport and anisotropy in SrIrO3 films.

Iridate oxides display exotic physical properties that arise from the interplay between a large spin-orbit coupling and electron correlations. Here, we present a comprehensive study of the effects of hydrostatic pressure on the electronic transport properties of SrIrO3 (SIO), a system that has recently attracted a lot of attention as potential correlated Dirac semimetal. Our investigations on untwinned thin films of SIO reveal that the electrical resistivity of this material is intrinsically anisotropic and controlled by the orthorhombic distortion of the perovskite unit cell. These effects provide another evidence for the strong coupling between the electronic and lattice degrees of freedom in this class of compounds. Upon increasing pressure, a systematic increase of the transport anisotropies is observed. The anomalous pressure-induced changes of the resistivity cannot be accounted for by the pressure dependence of the density of the electron charge carriers, as inferred from Hall effect measurements. Moreover, pressure-induced rotations of the IrO6 octahedra likely occur within the distorted perovskite unit cell and affect electron mobility of this system.

Design, characterization and in vitro evaluation of thin films enriched by tannic acid complexed by Fe(III) ions.

Materials based on carbohydrate polymers may be used for biomedical application. However, materials based on natural polymers have weak physicochemical properties. Thereby, there is a challenge to improve their properties without initiation of toxicity. The alternative method compared to toxic chemical agents' addition is the use of metal complexation method. In this study, chitosan/tannic acid mixtures modified by Fe(III) complexation are proposed and tested for potential applications as wound dressings. Thereby, surface properties, blood compatibility as well as platelet adhesion was tested. In addition, the periodontal ligament stromal cells compatibility studies were carried out. The results showed that the iron(III) addition to chitosan/tannic acid mixture improves properties due to a decrease in the surface free energy and exhibited a reduction in the hemolysis rate (below 5%). Moreover, cells cultured on the surface of films with Fe(III) showed higher metabolic activity. The current findings allow for the medical application of the proposed materials as wound dressings.

Human dioxin-inducible cytochrome P1-450: complementary DNA and amino acid sequence.

Induction of cytochrome P1-450 has been linked to susceptibility to certain chemically induced cancers in mouse and man. Treatment of the human cell line MCF-7 with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) results in high levels of aryl hydrocarbon (benzo[a]pyrene) hydroxylase (P1-450) activity. This cell line was used to isolate a human P1-450 full-length complementary DNA (cDNA) clone. The cDNA is 2566 nucleotides in length, encodes a polyadenylated messenger RNA (2.8 kilobases in length), and has a continuous reading frame producing a protein with 512 residues (molecular weight, 58,151). The human P1-450 cDNA and protein are 63 percent and 80 percent similar to mouse P1-450 cDNA and protein, respectively. Whereas the mouse TCDD-inducible P-450 gene subfamily has two members (P1-450 and P3-450), the human TCDD-inducible gene subfamily appears to have only one gene (P1-450).