Influence of scanning protocol on the accuracy of complete-arch digital implant scans: An in vitro study.

OBJECTIVE: This in-vitro study assessed the influence of two intraoral scanning (IOS) protocols on the accuracy (trueness and precision) of digital scans performed in edentulous arches. METHODS: Twenty-two abutment-level master casts of edentulous arches with at least four implants were scanned repeatedly five times, each with two different scanning protocols. Protocol A (IOS-A) consisted of scanning the edentulous arch before inserting the implant scan bodies, followed by their insertion and its subsequent digital acquisition. Protocol B (IOS-B) consisted of scanning the edentulous arch with the scan bodies inserted from the outset. A reference scan from each edentulous cast was obtained using a laboratory scanner. Trueness and precision were calculated using the spatial fit analysis, cross-arch distance, and virtual Sheffield test. Statistical analysis was performed using generalized estimating equations (GEEs). Statistical significance was set at α = .05. RESULTS: In the spatial fit test, the precision of average 3D distances was 45 µm (±23 µm) with protocol IOS-A and 25 µm (±10 µm) for IOS-B (p < .001), and the trueness of average 3D distances was 44 µm (±24 µm) with protocol IOS-A and 24 µm (±7 µm) for IOS-B (p < .001). Cross-arch distance precision was 59 µm (±53 µm) for IOS-A and 41 µm (±43 µm) for IOS-B (p = .0035), and trueness was 64 µm (±47 µm) for IOS-A and 50 µm (±40 µm) for IOS-B (p = .0021). Virtual Sheffield precision was 286 µm (±198 µm) for IOS-A and 146 µm (±92 µm) for IOS-B (p < .001), and trueness was 228 µm (±171 µm) for IOS-A and 139 µm (±92 µm) for IOS-B (p < .001). CONCLUSIONS: The IOS-B protocol demonstrated significantly superior accuracy. Placement of scan bodies before scanning the edentulous arch is recommended to improve the accuracy of complete-arch intraoral scanning.

Attention-deficit hyperactivity disorder and psychostimulant use in patients seeking dental care-Associations with common orofacial pain complaints.

BACKGROUND: Dental medicine should expand its scope to properly assess medical and psychosocial factors that might have an impact on patients' oral health. Based on previous literature and clinical experience, attention-deficit/hyperactivity disorder and psychostimulant medications might represent factors associated with orofacial pain symptoms. OBJECTIVE: The aim of the study was to assess whether common orofacial pain complaints such as jaw pain, jaw clicking, teeth clenching and headaches are more prevalent in dental patients who have an ADHD diagnosis and/or use psychostimulant medications. METHODS: Orofacial pain symptoms prevalence was compared among four groups from a sample of new patients seeking dental care at Tufts University School of Dental Medicine (n = 11 699) based on ADHD diagnosis and psychostimulants intake: G1: no ADHD, no stimulants; G2: yes ADHD, yes stimulants; G3: yes ADHD, no stimulants; G4: no ADHD, yes stimulants. RESULTS: In multivariable logistic regression models adjusting for age, gender, tobacco use, and alcohol consumption, significant differences were found for clenching (p < .0001), jaw pain (p < .0001), and headache (p < .0001). Compared to G1, two groups (G2 and G4) exhibited significantly higher odds of clenching and headaches, whereas only G2 exhibited significantly higher odds of jaw pain. CONCLUSIONS: In comparison with patients without ADHD and not taking psychostimulants medications, dental patients using psychostimulants with and without ADHD diagnosis report headaches and teeth clenching more frequently, while jaw pain is reported more frequently only by those taking psychostimulants with an ADHD diagnosis. Further research is necessary to assess the nature of these associations and their clinical relevance.

Evaluation of marginal and internal adaptation of veneers generated by the guided prosthetic tooth preparation system.

OBJECTIVE: This in vitro study aimed to assess and contrast the marginal and internal adaptation of all-ceramic prefabricated veneers manufactured via the FirstFit guided tooth preparation system against all-ceramic veneers produced using the chairside Computer-Aided Design/Computer Aided Manufacture (CAD/CAM) system following identical guided preparation protocols. MATERIALS AND METHODS: Two main groups were included, with 16 lithium disilicate veneers per group. Four typodonts were used for the test (FirstFit) and control CAD/CAM groups. Intraoral scans created master casts and preparation guides. Guides performed preparations on typodont teeth (two central incisors and two lateral incisors). Prepared teeth were scanned (CEREC Omnicam) to design and mill CAD/CAM veneers. Marginal gap thickness and cement space thickness were measured using light microscopy at four locations: marginal, cervical internal, middle internal, and incisal internal. RESULTS: No significant difference existed between groups for marginal adaptation (p = 0.058) or incisal internal adaptation (p = 0.076). The control group had significantly lower values for middle internal adaptation (p = 0.023) and cervical internal adaptation (p = 0.019). CONCLUSIONS: Guided preparation evaluation showed no significant differences in marginal or incisal internal adaptation. The CAD/CAM group had significantly lower middle and cervical internal adaptation values.

Post-partum cerebral venous sinus thrombosis: A case report.

INTRODUCTION: Cerebral venous sinus thrombosis (CVST) is a rare and life-threatening condition that may be encountered during pregnancy and puerperium. The diagnosis of CVST is a challenge because of its varied presentation. CASE REPORT: A 28-year-old woman presented with headache, projectile vomiting, and generalized tonic-clonic seizures 10 days after delivery by cesarean section. She had an uneventful antenatal period of 38 weeks of gestation. High clinical suspicion and the availability of magnetic resonance venography helped in making a diagnosis of CVST. She was successfully managed with a low-molecular-weight heparin (LMWH) and anti-epileptic therapy with no residual complications. DISCUSSION: Pregnancy induces several prothrombotic changes in the coagulation system that predispose to CVST. These changes persist for six to eight weeks after birth. Infection and cesarean section are the additional risk factors for CVST during puerperium. The symptoms of CVST depend on the sinuses and veins involved, raised intracranial pressure, and the extent of brain parenchymal injury. CONCLUSION: Greater awareness of the disease and the availability of imaging modalities have contributed to the early diagnosis and favorable outcomes in these cases. LMWH is the main stay of treatment in this disease.

Bandgaps of long-period polytypes of IV, IV-IV, and III-V semiconductors estimated with an Ising-type additivity model.

We apply an Ising-type model to estimate the bandgaps of the polytypes of group IV elements (C, Si, and Ge) and binary compounds of groups: IV-IV (SiC, GeC, and GeSi), and III-V (nitride, phosphide, and arsenide of B, Al, and Ga). The models use reference bandgaps of the simplest polytypes comprising 2-6 bilayers calculated with the hybrid density functional approximation, HSE06. We report four models capable of estimating bandgaps of nine polytypes containing 7 and 8 bilayers with an average error of ≲0.05 eV. We apply the best model with an error of <0.04 eV to predict the bandgaps of 497 polytypes with up to 15 bilayers in the unit cell, providing a comprehensive view of the variation in the electronic structure with the degree of hexagonality of the crystal structure. Within our enumeration, we identify four rhombohedral polytypes of SiC-9R, 12R, 15R(1), and 15R(2)-and perform detailed stability and band structure analysis. Of these, 15R(1) that has not been experimentally characterized has the widest bandgap (>3.4 eV); phonon analysis and cohesive energy reveal 15R(1)-SiC to be metastable. Additionally, we model the energies of valence and conduction bands of the rhombohedral SiC phases at the high-symmetry points of the Brillouin zone and predict band structure characteristics around the Fermi level. The models presented in this study may aid in identifying polytypic phases suitable for various applications, such as the design of wide-gap materials, that are relevant to high-voltage applications. In particular, the method holds promise for forecasting electronic properties of long-period and ultra-long-period polytypes for which accurate first-principles modeling is computationally challenging.

Diagnostic potential of nanoparticle aided assays for MUC16 and MUC1 glycovariants in ovarian cancer.

Our study reports the discovery and evaluation of nanoparticle aided sensitive assays for glycovariants of MUC16 and MUC1 in a unique collection of paired ovarian cyst fluids and serum samples obtained at or prior to surgery for ovarian carcinoma suspicion. Selected glycovariants and the immunoassays for CA125, CA15-3 and HE4 were compared and validated in 347 cyst fluid and serum samples. Whereas CA125 and CA15-3 performed poorly in cyst fluid to separate carcinoma and controls, four glycovariants including MUC16MGL , MUC16STn , MUC1STn and MUC1Tn provided highly improved separations. In serum, the two STn glycovariants outperformed conventional CA125, CA15-3 and HE4 assays in all subcategories analyzed with main benefits obtained at high specificities and at postmenopausal and early-stage disease. Serum MUC16STn performed best at high specificity (90%-99%), but sensitivity was also improved by the other glycovariants and CA15-3. The highly improved specificity, excellent analytical sensitivity and robustness of the nanoparticle assisted glycovariant assays carry great promise for improved identification and early detection of ovarian carcinoma in routine differential diagnostics.

Implications of COVID-19 on Thrombotic Profile of Severely Affected Patients.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is a novel viral disease that spread as a global pandemic in 2020 by infecting millions of people across the world. Its clinical prognosis is dependent on various coagulatory parameters since thrombotic events are frequently associated with infection severity. METHODS: A total of 383 COVID-19 patients enrolled in Rajiv Gandhi Super Specialty Hospital, Delhi, India, were included in the present retrospective study. Patients were divided into three categories, severe (n = 141), moderate (n = 138), and mild (n = 104) based on infection severity. Various thrombotic parameters and anticoagulant levels were measured in 70 patients and further analyzed. RESULTS: Coagulopathy is seen in COVID-19 patients (n = 70) with a significant increase in fibrinogen, D-dimer levels, and prothrombin time in patients with severe and moderate disease compared to patients with a mild infection. Approximately, 70% of patients with severe and moderate disease demonstrated fibrinogen levels higher than the standard reference range. 60.41% of patients with severe disease showed significantly higher D-dimer levels. Thrombotic parameters were notably elevated in the nonsurvivors group compared to COVID-19 survivors. Nearly, 91% of patients with severe infection had anticoagulant protein S levels below the reference range. CONCLUSION: COVID-19 infection severely impacts the blood coagulation cascade, which might lead to the manifestation of severe symptoms and increased mortality in patients.

The role of social media for patients with temporomandibular disorders: A content analysis of Reddit.

BACKGROUND: Social media is frequently used to discuss health topics among users. Reddit is a popular social media platform particularly suit for discussion about chronic illness because of its anonymity that allow users to express uninhibited feelings. Temporomandibular disorders (TMD) represent a chronic painful disorder which has been rarely studied in terms of social media discussion. OBJECTIVES: By exploring how Reddit is used to discuss about TMD, we aim to raise awareness to clinicians involved in TMD management about the online discussion on this topic. METHODS: A quantitative content analysis was performed on a pool of most relevant threads and comments about the topic "TMJ" on Reddit. Following a codebook, two independent coders assessed multiple clinically relevant variables. A third subject resolved eventual discrepancies. RESULTS: Reddit is mostly used by subjects with TMD asking for advice to other users about symptoms and treatment modalities. The most discussed causes of TMD were bruxism and dental occlusion, and the most discussed treatments were oral appliance therapy and complementary and alternative treatments. The most favourable opinions about treatment modalities were for self-care and behavioural therapy while the least favourable opinions were for surgery and irreversible dental treatments. CONCLUSIONS: Reddit represents an excellent data-mining platform to retrieve valuable information about health-related discussion by the community. Our findings suggest an overall alignment of such discussion with evidence-based science about TMD; however, to further increase this trend, we encourage healthcare provider to take an active role in the digital spread of scientifically valid information.

Potential association of COVID-19 and ABO blood group: An Indian study.

Coronavirus disease 2019 (COVID-19) transmits from person to person mainly through respiratory droplets and coughing. Infection severity ranges from asymptomatic and mild infection to those with moderate and severe symptoms which may lead to multiple organ failure and mortality. Infection severity largely depends on individual's immune response, age and co-morbidities. Present study categorized COVID-19 infected patients based on their infection severity and linked COVID-19 severity with age, gender and ABO blood group types. Clinical details of 383 COVID-19 patients were collected from Rajiv Gandhi Super Specialty hospital (RGSSH), India; divided into three groups; mild, moderate and severe patients, based on their symptoms. Present analysis revealed that age plays major role in infection severity, as the symptoms are more severe in patients above 45 years. Infection rate was higher in males compared to females. Most patients with A(+ve) and B(+ve) blood group were severely affected compared to those of blood group type O(+ve) and AB(+ve). O(+ve) blood group was least represented in severe patients. Present findings could be helpful in generating awareness amongst the population regarding susceptibility towards the COVID-19 infection. This supportive information would help clinicians and health workers to propose new strategies and tactical solution against COVID-19 infection.

Influence of smoking history on the perception of radiation-induced dysgeusia/hypogeusia in patients with head and neck cancer.

OBJECTIVES: This investigation aimed to assess the effect of smoking on the onset and resolution of dysgeusia/hypogeusia in head and neck cancer (HNC) patients receiving radiotherapy (XRT). MATERIALS AND METHODS: This is a retrospective cohort investigation of HNC patients treated with XRT. Data collected from the patients' medical records included demographics, primary cancer diagnoses, HNC therapeutic modalities, smoking status, and dates of onset/resolution of dysgeusia/hypogeusia. RESULTS: A 103 met inclusion criteria, of which 61.8% developed dysgeusia/hypogeusia. Mean age was 58.3 ± 12.9 and 66% were either former or current smokers. Never smokers seemed to be at higher, but statistically insignificant, the risk for developing dysgeusia/hypogeusia than former or current smokers [HR 1.05 and 1.66; 95% CI (0.60, 1.84) and (0.85, 3.24)]. They were also less likely to recover when compared to former smokers [HR 0.74; 95% CI (0.39, 1.39)]. Although statistically insignificant, never smokers showed rapid dysgeusia/hypogeusia onset after XRT compared to former or current smokers (median 14 days versus 22 and 9 days, respectively; p = 0.25). Never smokers showed quicker but statistically insignificant, recovery time compared to former or current smokers (median 113 days versus 149 and 238 days, respectively; p = 0.57). CONCLUSION: Although results lacked statistical significance, never smokers receiving XRT were prone to higher risk and faster onset of dysgeusia/hypogeusia than former and current smokers.

Deep Learning-Based Diabetic Retinopathy Severity Grading System Employing Quadrant Ensemble Model.

The diabetic retinopathy accounts in the deterioration of retinal blood vessels leading to a serious compilation affecting the eyes. The automated DR diagnosis frameworks are critically important for the early identification and detection of these eye-related problems, helping the ophthalmic experts in providing the second opinion for effectual treatment. The deep learning techniques have evolved as an improvement over the conventional approaches, which are dependent on the handcrafted feature extraction. To address the issue of proficient DR discrimination, the authors have proposed a quadrant ensemble automated DR grading approach by implementing InceptionResnet-V2 deep neural network framework. The presented model incorporates histogram equalization, optical disc localization, and quadrant cropping along with the data augmentation step for improving the network performance. A superior accuracy performance of 93.33% is observed for the proposed framework, and a significant reduction of 0.325 is noticed in the cross-entropy loss function for MESSIDOR benchmark dataset; however, its validation utilizing the latest IDRiD dataset establishes its generalization ability. The accuracy improvement of 13.58% is observed when the proposed QEIRV-2 model is compared with the classical Inception-V3 CNN model. To justify the viability of the proposed framework, its performance is compared with the existing state-of-the-art approaches and 25.23% of accuracy improvement is observed.

Social Stigma of COVID-19 Experienced by Frontline Healthcare Workers of Department of Anaesthesia and Critical Care of a Tertiary Healthcare Institution in Delhi.

BACKGROUND: Social stigma is associated with Coronavirus Disease-2019 (COVID-19) particularly against people who have contracted the disease or have come in contact with it. There is paucity of studies regarding the prevalence of social stigma against healthcare workers (HCWs) in COVID-19 hospitals in India. The objective of this study was to measure social stigma faced by frontline HCWs of Department of Anaesthesia and Critical Care in a COVID-19 hospital and to assess the relationship between sociodemographic characteristics and social stigma. PATIENTS AND METHODS: A cross-sectional study using a questionnaire (sociodemographic characteristics along with modified Berger HIV Stigma Scale) was conducted from October 10, 2020 to October 30, 2020, in the Department of Anaesthesia and Critical Care. The survey was distributed among frontline HCWs using Google Forms as well as Bilingual Physical Form. Total stigma and subgroups of stigma scale were measured for different sociodemographic parameters and compared. Data were presented as mean ± standard deviation. p-value <0.05 was taken as significant. RESULTS: Out of 120 frontline HCWs participated in the study, 68 (56.6%) reported severe level of COVID-19-related stigma. The mean score of COVID-19-related stigma was 41 + 7.69. Mean scores for subgroups of stigma scale, i.e., personalized stigma, disclosure concerns, negative self-image, and concerns with public attitude, were 15.60 + 4.01, 6.68 + 3.21, 5.46 + 3.22, and 13.25 + 2.44, respectively. In the univariate analysis, the overall COVID-19-related stigma scores were associated with age >30 years, male gender, lower designation (technicians and nursing orderly), lesser education, and married HCWs. In logistic regression model, only male gender was significantly associated with severity of COVID-19 stigma. CONCLUSION: This study concluded that more than half of frontline HCWs in the Department of Anaesthesia and Critical Care experienced severe social stigma during COVID-19 pandemic, with highest stigma in concerns with public attitude subgroup. Severity of stigma was associated with age, male gender, designation, education, and marital status of HCW. HIGHLIGHTS: Frontline HCWs of Department Anaesthesia and Critical Care experienced significant stigma related to COVID-19. HOW TO CITE THIS ARTICLE: Jain S, Das AK, Talwar V, Kishore J, Heena, Ganapathy U. Social Stigma of COVID-19 Experienced by Frontline Healthcare Workers of Department of Anaesthesia and Critical Care of a Tertiary Healthcare Institution in Delhi. Indian J Crit Care Med 2021;25(11):1241-1246.

A longitudinal analysis of CA125 glycoforms in the monitoring and follow up of high grade serous ovarian cancer.

OBJECTIVE: Cancer antigen 125 (CA125) is generally considered the gold standard of biomarkers in the diagnosis and monitoring of high grade serous ovarian carcinoma (HGSC). We recently reported, that two CA125 glycoforms (CA125-STn and CA125-MGL) have a high specificity to HGSC and further hypothesized, that these cancer specific glycoforms are feasible candidates as biomarkers in HGSC treatment and follow up. METHODS: Our cohort consisted of 122 patients diagnosed with HGSC. Serum samples were collected longitudinally at the time of diagnosis, during treatment and follow up. Serum levels of CA125, CA125-STn and CA125-MGL were determined and compared or correlated with different end points (tumor load assessed intraoperatively, residual disease, treatment response, progression free survival). RESULTS: Serum CA125-STn levels at diagnosis differentiated patients with low tumor load and high tumor load (p = 0,030), indicating a favorable detection of tumor volume. Similarly, the CA125-STn levels at diagnosis were significantly lower in patients with subsequent complete cytoreduction than in patients with suboptimal cytoreduction (p = 0,025). Conventional CA125 did not differentiate these patients (p = 0,363 and p = 0,154). The CA125-STn nadir value predicted the progression free survival of patients. The detection of disease relapse was improved with CA125-STn, which presented higher fold increase in 80,0% of patients and earlier increase in 37,0% of patients. CONCLUSIONS: CA125-STn showed promise as a useful biomarker in the monitoring and follow up of patients with HGSC utilizing a robust and affordable technique. Our findings are topical as a suitable indicator of tumor load facilitates patient selection in an era of new targeted therapies.

SWI/SNF interacts with cleavage and polyadenylation factors and facilitates pre-mRNA 3' end processing.

SWI/SNF complexes associate with genes and regulate transcription by altering the chromatin at the promoter. It has recently been shown that these complexes play a role in pre-mRNA processing by associating at alternative splice sites. Here, we show that SWI/SNF complexes are involved also in pre-mRNA 3' end maturation by facilitating 3' end cleavage of specific pre-mRNAs. Comparative proteomics show that SWI/SNF ATPases interact physically with subunits of the cleavage and polyadenylation complexes in fly and human cells. In Drosophila melanogaster, the SWI/SNF ATPase Brahma (dBRM) interacts with the CPSF6 subunit of cleavage factor I. We have investigated the function of dBRM in 3' end formation in S2 cells by RNA interference, single-gene analysis and RNA sequencing. Our data show that dBRM facilitates pre-mRNA cleavage in two different ways: by promoting the association of CPSF6 to the cleavage region and by stabilizing positioned nucleosomes downstream of the cleavage site. These findings show that SWI/SNF complexes play a role also in the cleavage of specific pre-mRNAs in animal cells.

Structure-guided design of antibacterials that allosterically inhibit DNA gyrase.

A series of DNA gyrase inhibitors were designed based on the X-ray structure of a parent thiophene scaffold with the objective to improve biochemical and whole-cell antibacterial activity, while reducing cardiac ion channel activity. The binding mode and overall design hypothesis of one series was confirmed with a co-crystal structure with DNA gyrase. Although some analogs retained both biochemical activity and whole-cell antibacterial activity, we were unable to significantly improve the activity of the series and analogs retained activity against the cardiac ion channels, therefore we stopped optimization efforts.

Effect of Adjuvant Homeopathy with Usual Care in Management of Thrombocytopenia Due to Dengue: A Comparative Cohort Study.

BACKGROUND: Dengue is an emerging threat to public health. At present, no clear modalities are available for the prevention and management of thrombocytopenia due to dengue. This article reports the clinical outcomes of integrative homeopathic care in a hospital setting during a severe outbreak of dengue in New Delhi, India, during the period September to December 2015. METHODS: Based on preference, 138 patients received a homeopathic medicine along with usual care (H+UC), and 145 patients received usual care (UC) alone. Assessment of thrombocytopenia (platelet count < 100,000/mm3) was the main outcome measure. Kaplan-Meier analysis enabled comparison of the time taken to reach a platelet count of 100,000/mm3. RESULTS: There was a statistically significantly greater rise in platelet count on day 1 of follow-up in the H+UC group compared with UC alone (mean difference = 12,337; 95% confidence interval [CI], 5,421 to 19,252; p = 0.001). This trend persisted until day 5 (mean difference = 14,809; 95% CI, 1,615 to 28,004; p = 0.02). The time taken to reach a platelet count of 100,000/mm3 was nearly 2 days earlier in the H+UC group compared with UC alone (H+UC: 3.44 days ± standard error of the mean [SEM] 0.18; 95% CI, 3.08 to 3.80; UC: 5.28 days ± SEM 0.29; 95% CI, 4.71 to 5.86; p < 0.001). CONCLUSION: These results suggest a positive role of adjuvant homeopathy in thrombocytopenia due to dengue. Randomized controlled trials may be conducted to obtain more insight into the comparative effectiveness of this integrative approach.

Clinical features and response to botulinum toxin in primary and secondary hemifacial spasm.

BACKGROUND: Hemifacial spasm (HFS) is a hyperkinetic movement disorder of adults. The condition is usually primary, but may be secondary to facial nerve damage, and responds well to botulinum toxin therapy. AIM: To study the demographic and clinical features of primary and secondary HFS and assess its response to botulinum toxin therapy. MATERIALS AND METHODS: A retrospective study of 40 patients of primary (33) and secondary (7) HFS, who attended our botulinum toxin clinic over the last 18 months, was conducted. We collected the data including the demographic profile, clinical features of primary and secondary HFS, severity measured by Likert scale, etiology, details of magnetic resonance imaging (MRI) of the brain, and a detailed account of the botulinum toxin injection. RESULTS: Thirty-three out of the 40 patients had primary HFS. The mean age at presentation was 48.4 ± 12.6 years whereas the mean duration of symptoms was 57.4 ± 39.3 (6-144) months. The onset of spasm on the upper part of face was seen in 31 patients (77.5%). An ipsilateral ear click was found in 17 (42.5%) patients. Mild spasms were seen in 18 patients, whereas 12 patients had severe spasms. The severity of spasm was lower in patients with secondary HFS. Five out of 22 magnetic resonance imaging (MRI) results showed an abnormality. The mean dosage of botulinum toxin was 21.86 ± 4.19 units in primary spasm and 17 ± 4.16 units in secondary spasm (P =0.018). The mean duration of response was 112.6 ± 55.7 days (median: 90 days; range: 30-240 days) in primary spasm and 135 ± 63.6 days (median: 135 days; range: 90-180 days) in secondary spasm (P = 0.29). CONCLUSION: Ipsilateral auditory clicks are fairly common in primary and secondary HFS. The patients with secondary HFS have a milder intensity of disease and they may have the onset of spasm from the upper part of face. Both primary as well as secondary HFS patients respond well to botulinum toxin injection; however, the adverse effects are more likely to occur in secondary HFS, and therefore, these patients require lower dosages of toxin.

Distinguishing between biochemical and cellular function: Are there peptide signatures for cellular function of proteins?

The genome annotation and identification of gene function depends on conserved biochemical activity. However, in the cell, proteins with the same biochemical function can participate in different cellular pathways and cannot complement one another. Similarly, two proteins of very different biochemical functions are put in the same class of cellular function; for example, the classification of a gene as an oncogene or a tumour suppressor gene is not related to its biochemical function, but is related to its cellular function. We have taken an approach to identify peptide signatures for cellular function in proteins with known biochemical function. ATPases as a test case, we classified ATPases (2360 proteins) and kinases (517 proteins) from the human genome into different cellular function categories such as transcriptional, replicative, and chromatin remodelling proteins. Using publicly available tool, MEME, we identify peptide signatures shared among the members of a given category but not between cellular functional categories; for example, no motif sharing is seen between chromatin remodelling and transporter ATPases, similarly between receptor Serine/Threonine Kinase and Receptor Tyrosine Kinase. There are motifs shared within each category with significant E value and high occurrence. This concept of signature for cellular function was applied to developmental regulators, the polycomb and trithorax proteins which led to the prediction of the role of INO80, a chromatin remodelling protein, in development. This has been experimentally validated earlier for its role in homeotic gene regulation and its interaction with regulatory complexes like the Polycomb and Trithorax complex. Proteins 2017; 85:682-693. © 2016 Wiley Periodicals, Inc.

Fluoride exposure abates pro-inflammatory response and induces in vivo apoptosis rendering zebrafish (Danio rerio) susceptible to bacterial infections.

The present study describes the immunotoxic effect of chronic fluoride exposure on adult zebrafish (Danio rerio). Zebrafish were exposed to fluoride (71.12 mg/L; 1/10 LC50) for 30 d and the expression of selected genes studied. We observed significant elevation in the detoxification pathway gene cyp1a suggesting chronic exposure to non-lethal concentration of fluoride is indeed toxic to fish. Fluoride mediated pro-oxidative stress is implicated with the downregulation in superoxide dismutase 1 and 2 (sod1/2) genes. Fluoride affected DNA repair machinery by abrogating the expression of the DNA repair gene rad51 and growth arrest and DNA damage inducible beta a gene gadd45ba. The upregulated expression of casp3a coupled with altered Bcl-2 associated X protein/B-cell lymphoma 2 ratio (baxa/bcl2a) clearly suggested chronic fluoride exposure induced the apoptotic cascade in zebrafish. Fluoride-exposed zebrafish when challenged with non-lethal dose of fish pathogen A. hydrophila revealed gross histopathology in spleen, bacterial persistence and significant mortality. We report that fluoride interferes with system-level output of pro-inflammatory cytokines tumour necrosis factor-α, interleukin-1ß and interferon-γ, as a consequence, bacteria replicate efficiently causing significant fish mortality. We conclude, chronic fluoride exposure impairs the redox balance, affects DNA repair machinery with pro-apoptotic implications and suppresses pro-inflammatory cytokines expression abrogating host immunity to bacterial infections.

Predictors and outcome of obstetric admissions to intensive care unit: A comparative study.

This descriptive observational study was carried out in Guru Teg Bahadur Hospital to identify predictors and outcome of obstetric admission to Intensive Care Unit (ICU). Ninety consecutive pregnant patients or those up to 42 days of termination of pregnancy admitted to ICU from October 2010 to December 2011 were enrolled as study subjects with selection of a suitable comparison group. Qualitative statistics of both groups were compared using Pearson's Chi-square test and Fisher's exact test. Odds ratio was calculated for significant factors. Low socioeconomic status, duration of complaints more than 12 h, delay at intermediary facility, and peripartum hysterectomy increased probability of admission to ICU. High incidence of obstetric admissions to ICU as compared to other countries stresses on need for separate obstetric ICU. Availability of high dependency unit can decrease preload to ICU by 5%. Patients with hemorrhagic disorders and those undergoing peripartum hysterectomy need more intensive care.