Effect of Sildenafil Citrate on Pulmonary Arterial Systolic Pressure and Sub-maximal Exercise Capacity in Chronic Obstructive Pulmonary Disease.

Background Pulmonary hypertension (PH) often complicates Chronic Obstructive Pulmonary Disease (COPD). Sildenafil reduces pulmonary arterial pressure associated with multitude of diseases. Objective To evaluate the use of Sildenafil in Pulmonary Hypertension associated with COPD. Method This randomized control study enrolled 72 patients: 61 completed the study. Thirtypatients with COPD received Sildenafil 25 mg thrice daily and 31 patients with COPD received optimal medical therapy for four weeks. Symptom assessment and dyspnoea grading was done with modified Borg scale and Modified Medical Research Council (MMRC) grade. The functional assessment was done with WHO functional classification. The estimation of pulmonary arterial systolic pressure and six minute walking distance was done before and after four weeks of the administration of therapy in both groups. Adverse reaction profiling was done for Sildenafil. The primary outcomes were the changes in pulmonary arterial systolic pressure and six minute walk test. The secondary outcomes were change in modified Borg scale for dyspnoea, MMRC grading and WHO functional class. Result The mean decrease in pulmonary arterial systolic pressure in Sildenafil group was significant as compared to controls (9.87+7.84 mmHg Vs 5.93+7.44 mmHg, P=0.048). The mean increase in six minute walk distance was significantly more in cases as compared to controls (48.13+25.79 m Vs 32.59+32.96 m,P=0.047). The changes in modified Borg scale was not significant (1.20+1.92 to 1.55+1.23; P=0.401). There was significant changes in MMRC grade (p=0.037). There was no significant change in WHO functional class after four weeks (p=0.071). Conclusion Sildenafil marginally decreased pulmonary arterial systolic pressure and increased six minute walk distance in COPD patients. It improved MMRC grading without affecting modified Borg's Scale and WHO functional class.

Manipulation of BCG vaccine: a double-edged sword.

Mycobacterium bovis Bacillus Calmette-Guérin (BCG), an attenuated vaccine derived from M. bovis, is the only licensed vaccine against tuberculosis (TB). Despite its protection against TB in children, the protective efficacy in pulmonary TB is variable in adolescents and adults. In spite of the current knowledge of molecular biology, immunology and cell biology, infectious diseases such as TB and HIV/AIDS are still challenges for the scientific community. Genetic manipulation facilitates the construction of recombinant BCG (rBCG) vaccine that can be used as a highly immunogenic vaccine against TB with an improved safety profile, but, still, the manipulation of BCG vaccine to improve efficacy should be carefully considered, as it can bring in both favourable and unfavourable effects. The purpose of this review is not to comprehensively review the interaction between microorganisms and host cells in order to use rBCG expressing M. tuberculosis (Mtb) immunodominant antigens that are available in the public domain, but, rather, to also discuss the limitations of rBCG vaccine, expressing heterologous antigens, during manipulation that pave the way for a promising new vaccine approach.

Six Minute Walk Distance and Reference Equations in Normal Healthy Subjects of Nepal.

BACKGROUND: The self-paced six minute walk test is a simple assessment for sub-maximal functional capacity. It correlates well with sophisticated tests and gives good prediction for morbidity, mortality, quality of life and pulmonary functions. OBJECTIVE: To evaluate six minute walk distance in healthy adults to identify reference values and formulate reference equations. METHOD: We conducted six minute walk test on 250 random volunteers at and above 18 years of age as per standard protocol. Age, gender, height and weight were measured. Pretest and post-test vital parameters were recorded including pulse oximetry. The six minute walking distance was identified in all subjects. Multiple regression analysis was done to formulate regression equations to predict six minute walking distance. This also correlated age, gender, height, weight, body mass index with six minute walking distance. RESULT: The mean six minute walking distance was 489±86 meters with males walking 509±82 meters and females 445±78 meters. Age, gender, weight and body mass index had significant contribution for prediction of six minute walking distance. Gender was the single most important predictor. Height had the least significance. Depending on coefficients of these variables we formulated three regression equations and tested them for accurate prediction. The two best equations were identified as: Predicted SMWD = 395-1.5xAge+2.47xWT-35.89xGender and Predicted SMWD = 440-1.82xAge-53.07xGender+5.12xBMI. CONCLUSION: Gender, age and height are the most important predictors of six minute walking distance. Reference values and equations for both genders, different age groups with varying weights were derived for local population.

Behavioral Patterns Toward Preventive Dental Care at School Dental Camps: An Observational Study in Bengaluru.

Background Dental behavior management problems of children towards preventive dental care at school dental camps in India remain largely undocumented. This study aimed to assess such behavior patterns in preschool and school-age children at a school dental health camp. Materials and methods The cross-sectional study included 462 children, with 261 children each in the preschool (three to five years old) and school (six to 12 years old) age groups in Bengaluru. On the school dental camp day, their behavior and anxiety were gauged using the Frankl Behavior Rating Scale and the Raghavendra, Madhuri, and Sujata Pictorial Scale, respectively. The Chi-square test was used to uncover predictive variables for children's behavior patterns toward preventive dental procedures at the dental school camps. Results A high prevalence of definitely negative Frankl Behavior Rating Scale ratings (59%, n=272) and dental anxiety (53%, n=245) were noted among the participants. Age, sex, the area of residence of the child, and the previous history of dental visits and treatment were predictors of their behavior at a school dental camp setup. Conclusion The present study gives an insight into the behavior of children towards preventive dental care at a school dental camp in a mobile dental van, stressing the need for behavior assessment before the treatment.

Depression, Anxiety, Stress, and Pain Severity in Patients With Recurrent Aphthous Stomatitis: A Cross-Sectional Study.

Background Recurrent aphthous stomatitis (RAS) is a chronic oral ulcerative condition with an elusive etiology that is associated with excruciating pain. Psychological factors have been suspected as a possible risk factor in its onset and development. Depression, anxiety, and stress play pivotal roles in how people experience pain. Hence, we aimed to explore the relationship between depression, anxiety, stress, and the severity of pain perceived due to recurrent ulcers in RAS patients. Materials and methods A cross-sectional comparative study was conducted on 248 patients, comprising 124 diagnosed with RAS and 124 healthy subjects without this oral condition. Patients from both of these groups were matched with regard to age and sex and recruited over a period of one year from a dental hospital in Bengaluru, India. Patients with any other oral lesions, painful oral conditions, or systemic and psychological illnesses were excluded. Depression, anxiety, and stress were assessed in these patients using the Depression Anxiety Stress Scale 21 (DASS-21). Utilizing a Visual Analog Scale, ulcer-related pain was assessed in patients with RAS. The data were analyzed using the chi-square test and Pearson's correlation test in IBM SPSS Statistics for Windows, Version 26.0 (released 2019, IBM Corp., Armonk, NY). Results The chi-square analysis showed that participants with RAS showed a statistically significant higher prevalence of extreme stress (n = 39, 31.5%), extreme anxiety (n = 82, 66.1%), and depression (n = 38, 30.6%) as opposed to those without this oral condition. A moderately positive correlation was observed in the Pearson's test between the severity of pain experienced and stress and anxiety (r = 0.65 and 0.60, respectively, p < 0.05), while a mild positive correlation was observed between the severity of pain and depression (r = 0.35, p < 0.05). Conclusion Depression, anxiety, and stress influenced the severity of pain in these lesions, dictating the need for a holistic approach that integrates psychological interventions in the management of such chronic oral conditions with psychological links.

A double-blind randomized controlled trial to compare the safety and efficacy of dexmedetomidine alone and in combination with ketamine in uncooperative and anxious paediatric dental patients requiring pulpectomy.

AIM: To compare the sedation regimen Dexmedetomidine alone and its combination with low dose Ketamine through intravenous route in terms of safety, efficacy and recovery profile in uncooperative paediatric dental patients requiring pulpectomy. MATERIAL AND METHODS: Thirty anxious and uncooperative 2-6-year-old children requiring pulpectomy in at least one primary molar were enrolled. Propofol was used as an induction agent. Drugs were administered through the intravenous route as per group assignment, i.e., Dexmedetomidine (1 µg/kg) with ketamine (0.5 mg/kg) administered over 10 min followed by a maintenance dose of Dexmedetomidine (0.2-0.8 µg/kg/h) in group A and Dexmedetomidine (1 µg/kg) administered over 10 min followed by a maintenance dose in group B. The sedation was titrated to achieve Houpt's overall behavior score of 4/5. The primary outcome measure was the successful completion of treatment. Secondary outcome measures were vital signs, quality of sedation, time need for the procedure, recovery time, intra-operative and post-operative adverse sequelae. RESULTS: Results showed that both of the regimens were similar in efficacy, safety and recovery profile. Also, the required dose of dexmedetomidine and the need for rescue boluses was similar in both of the study groups. CONCLUSION: Dexmedetomidine either alone or in combination with ketamine proved to be a safe and efficacious agent for paediatric dental sedation. No beneficial evidence of adding ketamine was observed.

Emergency Preparedness and Modish Practices among Primary Healthcare Delivery Systems Facilitated through Public-private Partnership Models in a South Indian Metropolitan City: A Descriptive Cross-sectional Study.

Background and aim: Access to health care is supposed to be a basic human right but the present scenario of the healthcare sector in India displays a large disparity in the healthcare services provided by the public and private sectors with wide variations in the infrastructure and services delivered by both sectors. Hence, public-private partnership (PPP) in healthcare delivery is an urgent and essential component that needs attention to ameliorate this gap. The aim of this study was to assess the current practices in healthcare services provided through PPPs in Bengaluru city. Materials and methods: A cross-sectional questionnaire survey was conducted among primary healthcare centers (PHC) run under PPP in Bengaluru city, Karnataka, India. The pretested self-designed structured questionnaire consisted of 18 items regarding the current practices of PPP at the primary healthcare level. Descriptive statistics were used to describe the data. Results: A total of 15 PPPs at the primary healthcare level were identified and included in the study. All of the participants provided basic healthcare services, some participants (33%) provided specialized services, and some (27%) mobile healthcare services. The overall impression of the medical officers in charge interviewed was that PPPs are better than individual endeavors by both public and private sectors. They also believed that it was important to have policies and guidelines in place to monitors aspects like the functioning of the setup, risk sharing, etc. Conclusion: The results indicated that all the participants were at the primary healthcare level and mostly involved in preventive practices. It is also important to look at venturing into services that provide curative services as well. Oral health, however, did not prominently feature at any point and is another area that requires attention. How to cite this article: Mukherji I, Eshwar S, Srivastava BK, et al. Emergency Preparedness and Modish Practices among Primary Healthcare Delivery Systems Facilitated through Public-private Partnership Models in a South Indian Metropolitan City: A Descriptive Cross-sectional Study. Int J Clin Pediatr Dent 2022;15(2):153-158.

Association of maternal risk factors with early childhood caries in schoolchildren of Moradabad, India.

BACKGROUND: Children who have caries in their primary teeth in infancy or toddlerhood tend to develop dental caries in their permanent dentition. Although risk indicators are helpful in identifying groups at risk, they give little information about the causes of difference in caries experience. AIM: To identify the association between maternal risk factors and early childhood caries among 3- to 5-year-old schoolchildren of Moradabad City, Uttar Pradesh, India. DESIGN: A total of 150 child-mother pairs participated in the study. The maternal risk factors were assessed by a pretested questionnaire. After obtaining the consent, the mothers and their children were clinically examined for dental caries using Radike criteria (1968). Saliva was collected from all the participating mothers for assessing the Streptococcus mutans level. RESULTS: Significant differences were found in mothers' caries activity, high level of S. mutans, educational level, socioeconomic status, frequency of maternal sugar consumption, and their child's caries experience (P < 0.001). CONCLUSIONS: Differences between children's situations in these underlying factors play out as consequential disparities in both their health and the health care they receive.

Expression and modulation of progesterone induced blocking factor (PIBF) and innate immune factors in human leukemia cell lines by progesterone and mifepristone.

Progesterone (P), required for successful pregnancy, influences autoimmune, infectious, and malignant diseases via adaptive and innate immune effects. P induces NK inhibitor progesterone induced blocking factor (PIBF) in CD8+ T cells. PIBF isoforms could permit solid tumor immune escape. Expression and modulation of PIBF and innate immune proteins by P in leukemia cells and leukocyte subpopulations have not been reported. Ten T, seven myeloid, six B, five epithelial, fibroblast BG9, G-CSF mobilized CD34+ stem cells, and peripheral blood mononuclear cells were screened for PIBF mRNA by RT-PCR, and protein by immunohistochemistry in SRIK-NKL, MOT, U937, HL60, R-CLL, MD-E, 729pH6neo, SRIH-B(ATL), SRIK-B(T-PLL), and MeWo. Cell lines expressing PIBF and exemplifying myeloid/monoblast, natural killer/T, and B lineages were cultured with and without 0.5 - 5 microM P or 0.5 - 0.05 microM mifepristone (RU486) for 24 h. Subsequently they were examined for changes in the expression of mRNA by RT-PCR and protein by immunohistochemistry for PIBF and some innate immune factors. All cells expressed PIBF mRNA; protein only in four (SRIK-NKL, U937, SRIK-B(T-PLL) and HL60) out of 10 cell lines tested. P increased and RU486 decreased PIBF in U937, SRIK-B(T-PLL) and SRIK-NKL. P upregulated TLR-4 in U937, and HNP1 - 3, LL-37, IRAK-2, and IRAK-4 in multiple lines and RU486 down regulated these. PIBF may be used by some leukemias to evade immune surveillance and is a potential therapeutic target. P may impact infection and autoimmunity via effects on LPS receptor, TLR signaling, and antimicrobial peptides.

New Vision for Improving the Oral Health Education of Visually Impaired Children- A Non Randomized Control Trial.

INTRODUCTION: Visually impaired people have poorer oral hygiene when compared to others. Therefore, there is a necessity for individual training by making awareness in oral care and plaque control so as to improve their oral hygiene. AIM: The aim of the present study was to assess the effectiveness of oral health innovative educative method among visually impaired children of Bengaluru city of India. MATERIALS AND METHODS: A non-randomized control trial was conducted among 40 visually impaired individuals attending special school for blind. The study was conducted for a duration of six months. Baseline data regarding oral health knowledge, attitude and practices was obtained through a questionnaire in Braille and oral plaque assessment was done using Silness and Loe plaque index (1964). Music based brushing technique, cast models and an oral health education talk and booklet in Braille was delivered stressing on importance of oral health. The results of Knowledge, Attitude and Practices (KAP) before and after health education were analysed using Chi-square test with SPSS version 22.0. RESULTS: The overall KAP was lower in the preintervention period among the visually impaired children with mean score of 6.98 while after the modified oral health education session, it was increased to a mean score of 14.68 which was statistically significant at p<0.001. There was a significant change in the oral plaque scores with 80% of the children having fair scores in the preintervention period to 30% in the postintervention period. CONCLUSION: This oral health education module showed good results which can be implemented to effectively increase the awareness about dental health.

Determinants of Tobacco Use and Prevalence of Oral Precancerous Lesions in Cab Drivers in Bengaluru City, India.

BACKGROUND: Tobacco is a most important risk factor for various types of cancer as well as some noncommunicable disease. Around 34.6% of Indian population consume tobacco. The tobacco consumption is higher in some vulnerable population such as drivers, daily wage laborers, and policemen. Tobacco consumption is known to cause oral cancers, and screening for oral cancer in these individuals is known to reduce mortality from cancer. The study was designed to assess the determinants of tobacco use and the prevalence of oral precancerous lesions in cab drivers. METHODS: This is a cross-sectional study among cab drivers at prepaid taxi counters in Bengaluru city. A total of 450 cab drivers were enrolled in the study, of which 225 cab drivers were interviewed during morning hours and remaining half at night time using a semi-structured questionnaire. All were screened for oral cancer/precancerous lesions. RESULTS: Nearly 70.88% of cab drivers were consuming tobacco in any form. Long working hours, working at night, and family members consuming tobacco were significant risk factors for tobacco use among cab drivers. Forty-eight drivers were detected to have oral precancerous lesions. CONCLUSIONS: It was very evident that long hours of driving and infrequent shifts played a greater role in acquiring the habit. Behavioral counseling and new laws need to be formed to limit the working hours in drivers to have an effective tobacco control.

Inhibition of deoxynucleotide-polymerizing enzyme activities of human leukemia lymphoblasts and simian sarcoma virus by tilorone and thirteen of its analogs.

Tilorone, which is 2,7-bis[2-(diethylamino)ethoxy]-9H-fluoren-9-one dihydrochloride, and 13 of its analogs inhibited human cellular DNA polymerases alpha and beta assayed with activated DNA as template and also cellular DNA polymerase gamma and DNA polymerase from simian sarcoma virus assayed with poly(A) (dT)12-18 as template. Terminal deoxynucleotidyltransferase (TdT), which has no template requirement, was not inhibited by any of the 14 compounds when d(A)12-18 or d(G)12-18 was used as initiator. Three compounds did not inhibit TdT assayed with activated DNA as initiator, but 11 compounds did, and these 11 compounds were generally less inhibitory to TdT than to the other DNA polymerases. The three compounds that did not inhibit TdT assayed with activated DNA but did inhibit the other DNA polymerases will be useful in the characterization of TdT activity. Modifications of the polycyclic ring structure of tilorone and the kinds of substituent groups attached to the ring structures influenced the degree of inhibition of all enzymes.

High terminal deoxynucleotidyl transferase activity in a new T-cell line (RPMI 8402) of acute lymphoblastic leukemia origin.

High activity of terminal deoxynucleotidyl transferase (terminal transferase) was found in a new "thymus-dependent" cell line (RPMI 8402) which is of acute lymphoblastic leukemia origin. This enzyme resembled the terminal transferase from other human cells in all its properties including Km (0.7 x 10(-6) m for dGTP). The high activity of this enzyme in RPMI 8402 and fresh acute leukemia lymphoblasts, in contrast to the low activity of this enzyme reported for "thymus-independent' cells, suggested that this cell line may have originated from leukemia cells. Moreover, the high activity of terminal transferase in RPMI 8402 cells should make feasible large-scale purification of this enzyme for detailed studies.

Deoxynucleotide-polymerizing enzyme activities in T- and B-cells of acute lymphoblastic leukemia origin.

All 5 thymus-dependent cell (T-cell) lines (Molt-3; Molt-4; RPMI-8402; CCRF-CEM; CCRF-HSB-2) and 7 thymus-independent cell (B-cell) lines (RPMI-8382, RPMI-8392, RPMI-8412, RPMI-8422, RPMI-8432, RPMI-8442, CCRF-SB) established so far from acute lymphoblastic leukemia patients were examined for deoxynucleotide polymerizing enzymes. All T- and B-cells had DNA polymerase gamma, DNA polymerase beta, and terminal deoxynucleotidyl transferase both in the soluble (the latter 2 enzymes only in small amounts) and chromatin fraction, whereas DNA polymerase alpha was found only in the soluble fraction. With respect to their sedimentation and chromatographic behavior, template-primer requirements, Km for deoxythymidine triphosphate or deoxyguanosine triphosphate divalent cation preference, effect of NaCI and inhibitors, the enzymes from T- and B-cells resembled each other and those from other mammalian cells. DNA polymerase alpha, beta, and gamma from T-cells like those from "fresh" acute lymphoblastic leukemia cells, were more thermolabile than those from B-cells or phytohemagglutinin-stimulated normal lymphocytes. In addition, the terminal deoxynucleotidyl transferase from the above cells was completely inactivated in 5 to 6 min at 50 degrees, whereas the DNA polymerase alpha, beta, and gamma retained considerable activity even after heating for 25 min at 50 degrees. DNA polymerase activity of the soluble fraction from T-cells was of the same magnitude as in B-cells when expressed on a DNA basis but twice that of B-cells when expressed on a protein basis. High terminal deoxynucleotidyl transferase activity, equivalent to that observed in acute lymphoblastic leukemia cells, was found in all T-cell lines that, when expressed on a DNA basis, was 30 to 100 times higher than the B-cell lines tested. These results support the suggestion of earlier investigators that T-cell lines examined here may have originated from leukemic cells.

Effect of bleomycin on deoxynucleotide-polymerizing enzymes from human cells.

DNA polymerases alpha and beta from Molt-4 cells are inhibited by bleomycin, whereas DNA polymerase gamma assayed with poly-(A)-(dT)12-18 as the template primer or terminal deoxynucleotidyl transferase assayed with activated DNA, poly(dA), (dG)12-18 or (dA)12-18 as the initiator are not inhibited by this antibiotic. Inhibition by bleomycin increased the Km for template DNA but not that for dTTP. Increasing amounts of bleomycin did not affect the Vmax for DNA polymerase alpha or beta when the amount of template DNA was varied but it reduced the Vmax for these enzymes when dTTP was varied. Moreover, the addition of extra template reversed the bleomycin inhibition but the addition of extra enzyme did not. Although dithiothreitol was required for bleomycin inhibition of DNA polymerase activity, bleomycin preincubated with dithiothreitol (or beta-mercaptoethanol) at pH 6.5 to 9.0 lost its inhibitory activity. This was not the case when DNA was also included in the preincubation mixture. The results obtained in this study indicate that bleomycin inhibits DNA polymerases alpha and beta by a thiol reagent-dependent interaction with the template. Thus, the antitumor activity of bleomycin may be greatly influenced by the concentration of sulfhydryl compounds and their proximity to DNA in the target cells.

Human T-cell leukemia virus I provirus and antibodies in a captive gorilla with non-Hodgkin's lymphoma.

Antibodies reactive against human T-cell leukemia virus I (HTLV-I) were detected by indirect immunofluorescence assay using MT-2 as target cells, enzyme linked immunosorbent assay screen and competition assay, and Western blot analysis in three sera (one collected in 1979) from a captive gorilla which developed diffuse histiocytic lymphoma in 1983. The sera from four other healthy gorillas housed separately were HTLV-I antibody negative. All sera were negative for HTLV-III antibodies by enzyme linked immunosorbent assay. Southern blot analysis of DNA from lymphoma tissue after digestion with BamHI and using complete HTLV-I genome probe gave one 10-kilobase fragment and a characteristic 1.05-kilobase internal fragment detected in all known HTLV-I isolates. These results indicate that the gorilla was infected with HTLV-I or a closely related simian virus several years before the development of lymphoma.

Human T-cell leukemia virus type I or a related retrovirus in patients with mycosis fungoides/Sézary syndrome and Kaposi's sarcoma.

Antibodies reactive with human T-cell leukemia virus type I (HTLV-I) proteins p19, p24, gp46, p56, and gp68 were detected in four of 27 patients with mycosis fungoides/Sézary syndrome (MF/SS) and one patient with Kaposi's sarcoma using radioimmunoprecipitation and Western blot analysis. Seroreactivity patterns to HTLV-I proteins of MF/SS sera were indeterminate or limited in comparison with sera of patients with adult T-cell leukemia/lymphoma. HTLV-I gag- and tax/rex-specific DNA was demonstrated in peripheral blood from three of the MF/SS patients and from the patient with Kaposi's sarcoma by the polymerase chain reaction. HTLV-I-specific DNA sequences were not detected in a cohort of seven seronegative MF/SS patients. The frequency of HTLV-I infection was four of 27 or 14.8% among the MF/SS patients, which is several hundredfold higher than in normal blood donors. The present data suggest a possible association of HTLV-I or a related retrovirus with mycosis fungoides/Sézary syndrome and Kaposi's sarcoma.