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1.
Morphologie ; 105(351): 308-315, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33579637

RESUMEN

BACKGROUND: Posterior layer of thoracolumbar fascia (PTLF) is the deep fascia of back of the trunk, which connects the trunk, upper limb and lower limb muscles. Very few cadaveric studies of posterior layer of thoracolumbar fascia (PTLF) are found in the literature, which mention the presence of nerve receptors in it but, quantification of the nerve receptors where not found. Providing the morphological and morphometrical data of PTLF may help the exercise physiologists, sports physicians, occupational health assistants and, physiotherapists to modify or invent new protocol of treatment to help the society. METHODS: In this study, twenty formalin embalmed human cadavers were used and we have documented the orientation of the PTLF and quantified the number of peripheral nerve endings at the different vertebral levels. RESULTS: Mean distance of PTLF from vertebral spines to the musculofascial junction was at thoracic region 3.38cm and 3.34cm; at lumbar region, it was 7.4cm and 7.36cm and at sacral region it was 2.98cm and 2.96cm on right and left side, respectively. The angulation of PTLF varies from 18-110 degrees at different vertebral levels. The microscopic data shows the thickness of PTLF and number of nerve endings in the sacral level is increased compared to that of thoracic vertebral levels. CONCLUSIONS: We have contributed the novel morphological and microscopical details to the limited existing data on PTLF. We also have provided the quantitative data of nerve fibers, which are possible nociceptors of PTLF.


Asunto(s)
Dolor de la Región Lumbar , Fascia , Humanos
2.
Acta Crystallogr Sect E Struct Rep Online ; 70(Pt 12): 580-3, 2014 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-25552997

RESUMEN

The title mol-ecular salt, C8H13N2 (+)·Br(-), crystallizes with two independent 3-amino-pyridinium cations and two bromide anions in the asymmetric unit (Z' = 2). In the pyridine ring, the N atom is alkyl-ated by a propyl group. The dihedral angle between the mean planes of the pyridinium ring and the propyl group is 84.84 (2)° in cation A, whereas the corresponding angle is 89.23 (2)° in cation B. In the crystal, the anions and cations are linked via N-H⋯Br and C-H⋯Br hydrogen bonds, forming chains propagating along [100].

3.
Acta Crystallogr Sect E Struct Rep Online ; 69(Pt 6): o884, 2013 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-23795060

RESUMEN

In the cation of the title salt, C8H11N2 (+)·Br(-), the dihedral angle between the planes of the pyridinium ring and the allyl group is 79.4 (3)°. In the crystal, N-H⋯Br and weak C-H⋯Br hydrogen bonds link the cations and anions, forming chains of alternating R 2 (1)(7) and R 4 (2)(8) rings, which run parallel to the c-axis direction. The crystal studied was an inversion twin with components in a 0.753 (12):0.247 (12) ratio.

4.
Acta Chim Slov ; 59(2): 242-8, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24061236

RESUMEN

Loxoprofen belongs to a class of Nonsteroidal anti-inflammatory drug acts by inhibiting isoforms of cyclo-oxygenase 1 and 2. In this study an improved RP-HPLC method was developed for the quantification of loxoprofen in pharmaceutical dosage form. For that purpose an experimental design approach was employed. Factors-independent variables (organic modifier, pH of the mobile phase and flow rate) were extracted from the preliminary study and as dependent variables three responses (loxoprofen retention factor, resolution between loxoprofen probenecid and retention time of probenecid) were selected. For the improvement of method development and optimization step, Derringer's desirability function was applied to simultaneously optimize the chosen three responses. The procedure allowed deduction of optimal conditions and the predicted optimum was acetonitrile: water (53:47, v/v), pH of the mobile phase adjusted at to 2.9 with ortho phosphoric acid. The separation was achieved in less than 4minutes. The method was applied in the quality control of commercial tablets. The method showed good agreement between the experimental data and predictive value throughout the studied parameter space. The optimized assay condition was validated according to International conference on harmonisation guidelines to confirm specificity, linearity, accuracy and precision.

5.
Bioinformation ; 18(4): 325-330, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36909691

RESUMEN

Breast cancer is one of the top three commonly caused cancers worldwide. Triple Negative Breast Cancer (TNBC), a subtype of breast cancer, lacks expression of the oestrogen receptor, progesterone receptor, and HER2. This makes the prognosis poor and early detection hard. Therefore, AI based neural models such as Binary Logistic Regression, Multi-Layer Perceptron and Radial Basis Functions were used for differential diagnosis of normal samples and TNBC samples collected from signal intensity data of microarray experiment. Genes that were significantly upregulated in TNBC were compared with healthy controls. The MLP model classified TNBC and normal cells with anaccuracy of 93.4%. However, RBF gave 74% accuracy and binary Logistic Regression model showed an accuracy of 90.0% in identifying TNBC cases.

6.
Langmuir ; 26(14): 12225-9, 2010 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-20462280

RESUMEN

Pdnp and Pd containing trimetallic nanoparticles (tnp) are synthesized by chemical method with cetyltrimethylammonium bromide as the capping agent. Compositionally, four different tnp are prepared and the particle sizes are characterized by UV-vis spectra, HR-TEM, and XRD measurements. The catalytic activities of Pdnp and tnp are tested using the Sonogashira C-C coupling reaction. The product yield and recyclability of the recovered catalysts are studied. tnp (1:1:1) exhibited better catalysis than Pdnp, which may be due to the concerted electronic effects of the Au-Ag core onto the Pd shell atoms.


Asunto(s)
Nanopartículas del Metal/química , Metales Pesados/química , Catálisis , Oro/química , Microscopía Electrónica de Rastreo , Paladio/química , Plata/química , Análisis Espectral , Difracción de Rayos X
9.
Bioinformation ; 16(7): 539-546, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32994679

RESUMEN

Sarcoidosis is often misdiagnosed as tuberculosis and consequently mistreated owing to inherent limitations in histopathological and radiological presentations. It is known that the differential diagnosis of Tuberculosis and Sarcoidosis is often non-trivial and requires expertise and experience from clinicians. Therefore, it is of interest to describe a multilayer neural network model to differentiate pulmonary tuberculosis from Sarcoidosis using signal intensity data from blood transcriptional microarray. Genes that are significantly upregulated in Pulmonary Tuberculosis and Sarcoidosis in comparison with healthy controls were used in the model. The model classified Pulmonary Tuberculosis and Sarcoidosis with 95.8% accuracy. The model also helps to identify gene markers that are differentially upregulated in the two clinical conditions.

10.
Bioinformation ; 16(2): 149-152, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32405166

RESUMEN

GenPop is a web based online cross platform tool developed to help Geneticist and Epidemiologist to deal with association studies in analyzing human population genetic data. The tool features include descriptive analysis such as Hardy-Weinberg equilibrium test, chi-square p-value and analysis of single nucleotide polymorphisms (SNPs) with multiple inheritance models such as dominant, recessive, allelic, genotype, odd's ratio and relative risk at 95% confidence interval and analysis of multiple SNPs including haplotype frequencies and linkage disequilibrium for a pair of biallelic markers. This is a user-driven human population genetic data analysis tool that is easily scalable and acceptable with multiple implementations of different algorithms. GenPop has been developed using PHP, JavaScript and with PHPExcel library to analyse the genetic data for case control studies.

11.
Indian J Tuberc ; 67(1): 8-14, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32192623

RESUMEN

BACKGROUND: Tuberculosis burden is still high and smoking prevalence among males has increased in India. It is found that increased morbidity, mortality and relapse among TB smokers. METHOD: Setting: Patients from two Revised National Tuberculosis Control Program Centres of Tamilnadu form the study population. OBJECTIVE: To compare the effectiveness of Bupropion therapy along with standard counselling versus enhanced counseling versus standard counseling for smoking cessation among TB patients. STUDY DESIGN: Cluster randomized effectiveness trial. PROCEDURE: Patients from each of the thirty-six Designated Microscopic Centres were randomly allocated to receive one of the three interventions using cluster randomization. Smoking cessation was assessed by self-reporting and confirmed by Carbon monoxide(CO) monitors, done at three-time points and TB treatment outcome at the end of ATT. RESULTS: Out of 517 male patients enrolled to the study, the smoking status is available only to 381 subjects. The proportion of patients who have quit smoking in drug, enhanced and standard arms at the end of treatment was 67%, 83% and 52% (P= < 0.001). There was no statistical significance in response to TB treatment between those who quit and those who did not (Favourable response 99.2% vs 97.6%). CONCLUSION: Both enhanced counselling arm and drug arm are effective strategies for smoking cessation among TB patients and their implementation in the TB programs are recommended.


Asunto(s)
Consejo/métodos , Agentes para el Cese del Hábito de Fumar/uso terapéutico , Cese del Hábito de Fumar/métodos , Fumar Tabaco/terapia , Tuberculosis Pulmonar/tratamiento farmacológico , Adulto , Antituberculosos/uso terapéutico , Bupropión/uso terapéutico , Humanos , India , Masculino , Persona de Mediana Edad , Motivación , Tuberculosis Pulmonar/complicaciones
12.
J Clin Immunol ; 29(5): 674-80, 2009 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-19472039

RESUMEN

INTRODUCTION: Association between inherited deficiencies of the complement components and immune complex disease indicates the importance of the complement system in the handling of circulating immune complexes. High levels of circulating immune complexes are seen in pulmonary tuberculosis. This study is, therefore, aimed to look at the concentration of circulating immune complexes, the status of complement-mediated immune complex handling, and the extent of complement activation in untreated pulmonary tuberculosis compared to treated pulmonary tuberculosis patients and healthy controls. RESULTS: High immune complex levels, decreased complement-mediated solubilization, and increased activation of the complement system were observed in untreated tuberculosis patients. CONCLUSIONS: The results obtained from the present study suggest that complement mediated solubilization is less in patients with tuberculosis, and this defective solubilization is likely to take part in a vicious cycle involving immune complex deposition and complement activation and, thus, may lead to disease progression depending on the nature of the defect.


Asunto(s)
Complejo Antígeno-Anticuerpo/biosíntesis , Complemento C3/metabolismo , Complemento C4/metabolismo , Mycobacterium tuberculosis/inmunología , Tuberculosis Pulmonar/inmunología , Adulto , Complejo Antígeno-Anticuerpo/sangre , Complejo Antígeno-Anticuerpo/genética , Biomarcadores/sangre , Activación de Complemento/genética , Complemento C3/genética , Complemento C3/inmunología , Complemento C4/genética , Complemento C4/inmunología , Citotoxicidad Inmunológica , Femenino , Humanos , Enfermedades del Complejo Inmune/congénito , Masculino , Persona de Mediana Edad , Monitorización Inmunológica , Mycobacterium tuberculosis/patogenicidad , Pronóstico , Tuberculosis Pulmonar/sangre , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/genética , Tuberculosis Pulmonar/fisiopatología , Virulencia
13.
Clin Immunol ; 128(1): 109-15, 2008 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-18434253

RESUMEN

Complement receptor 1 expressed on erythrocytes is involved in the transport of circulating immune complexes from the circulation to the mononuclear phagocyte system for safe disposal. The prevalence of complement receptor 1 genotypes and the association between circulating immune complexes and expression of complement receptor 1 on erythrocytes in pulmonary tuberculosis are not fully understood. Observations from this study showed increased occurrence of HH genotype in patients with pulmonary tuberculosis. Patients with tuberculosis had decreased erythrocyte complement receptor 1 and increased immune complex levels compared to healthy controls which also correlated with increasing severity of the disease. In addition, the expression of complement receptor 1 on erythrocytes correlated inversely with the levels of circulating immune complexes. This study suggests that the presence of HH genotype is high in pulmonary tuberculosis patients and the reduced complement receptor 1 in patients may be an acquired phenomenon related to disease pathogenesis.


Asunto(s)
Eritrocitos/metabolismo , Receptores de Complemento 3b/biosíntesis , Receptores de Complemento 3b/genética , Tuberculosis Pulmonar/genética , Tuberculosis Pulmonar/metabolismo , Adulto , Complejo Antígeno-Anticuerpo/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Citometría de Flujo , Genotipo , Humanos , Masculino , Reacción en Cadena de la Polimerasa , Polimorfismo Genético , Tuberculosis Pulmonar/sangre
14.
Int J Tuberc Lung Dis ; 12(2): 168-73, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18230249

RESUMEN

OBJECTIVE: To evaluate the utility of the tuberculin skin test (TST) in detecting latent and active tuberculosis (TB) among human immunodeficiency virus (HIV) infected patients in South India. DESIGN: TSTs and CD4 counts were collected from 631 HIV-infected individuals without active TB and 209 antiretroviral and anti-tuberculosis treatment-naïve HIV-infected patients with TB. We calculated the proportion of TST-positive individuals, as well as the sensitivity, specificity, positive predictive value (PPV) and negative predictive value of TST in the diagnosis of TB. RESULTS: Among subjects without active TB, 28% with a CD4 count <100 cells/microl vs. 43% of the total cohort had a TST >5 mm (P = 0.14), while the proportions with induration >10 mm were 14% vs. 36%, respectively (P < 0.01). Among those with active TB, using a 5 mm cut-off, the sensitivity was 42% for those with CD4 counts <200 cells/mul compared to 70% for those with CD4 counts >or=200 cells/microl (P < 0.001). The PPV for detecting active TB was 29%. CONCLUSIONS: TST is a poor predictor of both latent and active TB in HIV-infected individuals in TB endemic countries. Programmes offering treatment for latent TB should consider including all HIV-positive patients regardless of TST status, or use other indicators, such as CD4 count.


Asunto(s)
Infecciones por VIH/epidemiología , Prueba de Tuberculina , Tuberculosis/epidemiología , Adolescente , Adulto , Recuento de Linfocito CD4 , Comorbilidad , Femenino , Humanos , India , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Tuberculosis/tratamiento farmacológico
15.
Phytother Res ; 22(8): 1035-9, 2008 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-18618523

RESUMEN

The larvicidal activity of a petroleum ether extract of Zingiber officinale Roscoe (Zingiberaceae) was evaluated against Aedes aegypti L. and Culex quinquefasciatus Say (Diptera). Bioassay-guided fractionation led to the isolation of 4-gingerol (1), (6)-dehydrogingerdione (2) and (6)-dihydrogingerdione (3); the latter has not previously been reported from Z. officinale. The structures were established from infrared (IR), ultraviolet (UV), (1)H-nuclear magnetic resonance (NMR), (13)C-NMR and mass spectral data. Following a 24 h exposure, compounds 1-3 exhibited larvicidal activities against fourth instar larvae of A. aegypti (LC(50) 4.25, 9.80, 18.20 ppm) and C. quinquefasciatus (LC50 5.52, 7.66, 27.24 ppm), respectively. The results show that the most effective compound was 4-gingerol.


Asunto(s)
Aedes/efectos de los fármacos , Culex/efectos de los fármacos , Insecticidas/farmacología , Extractos Vegetales/farmacología , Zingiber officinale/química , Aedes/crecimiento & desarrollo , Animales , Fraccionamiento Químico , Culex/crecimiento & desarrollo , Relación Dosis-Respuesta a Droga , Insecticidas/química , Larva/efectos de los fármacos , Extractos Vegetales/química , Rizoma/química
16.
Natl Med J India ; 21(1): 3-8, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18472696

RESUMEN

BACKGROUND: Tuberculosis occurs in 60%-70% of HIV-positive persons in India. The outcome of HIV-positive patients treated with 6-month intermittent short course antituberculosis regimens in India is not well described. METHODS: This was a prospective observational feasibility study of 71 patients with HIV and tuberculosis who were treated with category I regimen of the Revised National Tuberculosis Control Programme (ethambutol, isoniazid, rifampicin and pyrazinamide thrice weekly for the initial 2 months followed by rifampicin and isoniazid thrice weekly for the next 4 months). Sputum was examined by smear and culture for Mycobacterium tuberculosis every month up to 24 months. Chest X-ray, CD4 cell count and viral load were done prior to and at the end of treatment. None of the patients received antiretroviral therapy. RESULTS: We present here the treatment response of patients with sputum culture-positive pulmonary tuberculosis to category I regimen. By efficacy analysis, among 43 patients treated with category I regimen, sputum smear conversion was observed in 79% and culture conversion in 82% at the second month. A favourable response was seen in 72% of patients. The mean (SD) CD4% fell from 12.6 (5.9) to 8.9 (4.9) (p < 0.001) with no significant change in mean (SD) CD4 cell count (169 [126] to 174 [158]; ns) at the end of treatment. Viral load change from 1.8 x 10(5) at baseline to 1.3 x 10(5) at the end of treatment was not statistically significant. Thirty-one patients, who completed the full course of treatment, were declared cured and were followed up for 24 months. Twelve had recurrent tuberculosis (39%); 16 of 43 (37%) patients had died by the end of 24 months, two-thirds due to causes other than tuberculosis. CONCLUSION: Though the early bacteriological response to intermittent short course antituberculosis regimen was satisfactory, the overall outcome was adversely affected by the high mortality (during and after completion of treatment) and recurrence rate among HIV-infected patients with tuberculosis. Immune status deteriorated in spite of antituberculosis treatment, highlighting the need for antiretroviral treatment in addition to antituberculosis treatment to improve the long term outcome. The results of this pilot study need to be confirmed by larger studies.


Asunto(s)
Antituberculosos/uso terapéutico , Infecciones por VIH/complicaciones , Tuberculosis/tratamiento farmacológico , Adolescente , Adulto , Recuento de Linfocito CD4 , Etambutol/uso terapéutico , Estudios de Factibilidad , Femenino , Infecciones por VIH/fisiopatología , Humanos , India , Isoniazida/uso terapéutico , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis , Estudios Prospectivos , Pirazinamida/uso terapéutico , Recurrencia , Rifampin/uso terapéutico , Resultado del Tratamiento , Tuberculosis/diagnóstico , Tuberculosis/etiología
17.
J Environ Biol ; 29(3): 287-90, 2008 May.
Artículo en Inglés | MEDLINE | ID: mdl-18972679

RESUMEN

Predatory efficiency of Diplonychus rusticus (Fabricius) was recorded at different prey density with different salinity ranges. When the salinity level (ppt) was increased, the predation rate of the bug decreased. Fifth nymphal stage showed higher predation in the 2, 4 and 6 ppt levels of salinityin both 1 hr and 24 hr period of exposure at prey densities 50, 100, 150 and 200. At prey density 150, adult bugs killed more prey in the 2 ppt level of salinity in both lhr and 24 hr treatments.


Asunto(s)
Hemípteros/fisiología , Conducta Predatoria , Cloruro de Sodio , Animales , Femenino , Masculino
18.
Indian J Clin Biochem ; 23(1): 85-8, 2008 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23105728

RESUMEN

This study was undertaken to evaluate the effects of n-3 fatty acid supplementation on blood glucose, lipid profile and cytokines in humans. Twenty adult healthy subjects were supplemented with 1g/day fish oil concentrate capsules for 2 weeks. Fasting blood samples were taken at baseline and again after 2 week intervention. Fish oil supplementation significantly lowered fasting serum concentrations of total cholesterol, triacylglycerol, very low density lipoprotein and low density lipoprotein (P < 0.01). Also high density lipoprotein increased significantly compared with baseline value (P < 0.01). Fish oil did not significantly altere the fasting blood glucose concentration but significantly reduced the serum cytokines (P < 0.001). This study demonstrated that eicosapentanoic acid (EPA) and docosahexaenoic acid (DHA) supplementation altered serum lipids, lipoprotein and cytokine concentrations in normal human subjects even at the small dose of 660 mg of EPA plus DHA per day. It appears that EPA plus DHA can be a safe and perhaps beneficial supplement to inflammatory diseases.

19.
J Clin Invest ; 99(3): 513-9, 1997 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-9022086

RESUMEN

Sensory nerves play an important role in airway disease by mediating central reflexes such as cough, and local axon reflexes resulting in the peripheral release of neuropeptides. We have tested whether the benzimidazolone compound, NS1619, an opener of large conductance calcium-activated potassium (BK Ca) channels, inhibits the activity of sensory fibers, and central and local airway reflexes in guinea pig airways. In in vitro single fiber recording experiments, NS1619 applied to identified receptive fields in the trachea inhibited the firing of A(delta)-fibers evoked by hypertonic saline and distilled water, and bradykinin-evoked firing of C-fibers. Electrically evoked nonadrenergic noncholinergic contractions of isolated bronchi mediated by the release of neurokinin A (NKA) from C-fibers, but not those elicited by exogenous NKA, were inhibited by NS1619. These effects of NS1619 were prevented by iberiotoxin, a selective blocker of BK Ca channels. In conscious guinea pigs, cough evoked by aerosolized citric acid was also inhibited by NS1619. These data show that BK Ca channel activation inhibits sensory nerve activity, resulting in a reduction of both afferent and efferent function. BK Ca channel openers may therefore be of potential benefit in reducing neurogenic inflammation and central reflexes seen during inflammatory conditions of the airways, and may represent a new class of antitussive drug.


Asunto(s)
Bencimidazoles/farmacología , Ganglios Sensoriales/efectos de los fármacos , Ganglios Sensoriales/fisiología , Canales de Potasio/efectos de los fármacos , Canales de Potasio/fisiología , Vías Aferentes/efectos de los fármacos , Animales , Bencimidazoles/antagonistas & inhibidores , Bradiquinina/farmacología , Bronquios/inervación , Pruebas de Provocación Bronquial , Ácido Cítrico/farmacología , Tos/inducido químicamente , Vías Eferentes/efectos de los fármacos , Cobayas , Técnicas In Vitro , Inflamación/tratamiento farmacológico , Masculino , Neuroquinina A/farmacología , Péptidos/farmacología , Tráquea/inervación
20.
J Microbiol Methods ; 68(3): 536-42, 2007 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17173989

RESUMEN

The mechanical pressure exerted during centrifugation and the chemical pressure experienced when sputum specimens are processed, leave the tubercle bacilli in the sputum unsuitable for rapid detection especially in phage based assays. Thus, growing Mycobacterium tuberculosis in broth, at least overnight, is mandatory for allowing the tubercle bacilli to recoup. During this time the surviving colonizing flora grow faster and overgrow tubercle bacilli interfering with TB diagnosis. In the present study normal flora surviving the action of 4% NaOH was isolated and characterized. Phages capable of killing 14 different species representing this normal flora were isolated from soil and sewage samples and characterized. A novel and bio-friendly approach to treat sputum samples with a cocktail of three phages capable of killing most of the 14 representative organisms and not infecting mycobacteria is explored to control the overgrowth of colonizing bacteria in broth culture. While 26 of the 100 sputum samples processed by modified Petroff's procedure showed growth of colonizing flora on blood agar, all of them when grown in broth overnight showed mixed, confluent growth. The addition of phagebiotics controlled them all, showing a significant reduction in colony forming units but resulting in few discrete colonies in 54 samples. Isolation of phages capable of controlling these surviving organisms and including them in the phagebiotics mixture should lead to the control of colonizing bacteria effectively.


Asunto(s)
Bacteriófagos/fisiología , Bacterias Gramnegativas/crecimiento & desarrollo , Bacterias Grampositivas/crecimiento & desarrollo , Mycobacterium tuberculosis/aislamiento & purificación , Esputo/microbiología , Tuberculosis Pulmonar/diagnóstico , Técnicas Bacteriológicas , Bacteriófagos/clasificación , Medios de Cultivo , Bacterias Gramnegativas/virología , Bacterias Grampositivas/virología , Lisogenia , Factores de Tiempo
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