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1.
Ticks Tick Borne Dis ; 15(3): 102329, 2024 May.
Article in English | MEDLINE | ID: mdl-38484538

ABSTRACT

Maps of the distribution of medically-important ticks throughout the US remain lacking in spatial and temporal resolution in many areas, leading to holes in our understanding of where and when people are at risk of tick encounters, an important baseline for informing public health response. In this work, we demonstrate the use of Bayesian Experimental Design (BED) in planning spatiotemporal surveillance of disease vectors. We frame survey planning as an optimization problem with the objective of identifying a calendar of sampling locations that maximizes the expected information regarding some goal. Here we consider the goals of understanding associations between environmental factors and tick presence and minimizing uncertainty in high risk areas. We illustrate our proposed BED workflow using an ongoing tick surveillance study in South Carolina parks. Following a model comparison study based on two years of initial data, several techniques for finding optimal surveys were compared to random sampling. Two optimization algorithms found surveys better than all replications of random sampling, while a space-filling heuristic performed favorably as well. Further, optimal surveys of just 20 visits were more effective than repeating the schedule of 111 visits used in 2021. We conclude that BED shows promise as a flexible and rigorous means of survey design for vector control, and could help alleviate pressure on local agencies by limiting the resources necessary for accurate information on arthropod distributions. We have made the code for our BED workflow publicly available on Zenodo to help promote the application of these methods to future surveillance efforts.


Subject(s)
Ticks , Animals , Humans , United States , Bayes Theorem , Southeastern United States/epidemiology
2.
J Neonatal Perinatal Med ; 16(4): 701-708, 2023.
Article in English | MEDLINE | ID: mdl-38073400

ABSTRACT

BACKGROUND: Neonatal hypothermia is a drop in the newborn's core temperature less than 36.5°C. It is crucial in neonatal morbidity and mortality, particularly in preterm infants. This research aimed to assess the incidence and risk factors of neonatal hypothermia and its effect on neonatal mortality and short-term morbidity during Neonatal Intensive Care Unit (NICU) admission. METHODS: This observational study was conducted on all neonates admitted to the NICU at Benha University Hospital. The core temperature was measured on admission for all admitted neonates and were followed up to assess the impact of hypothermia on short-term outcomes and mortality. RESULTS: A total of 323 neonates were admitted to the NICU throughout the research period. Thirty-five cases were excluded due to congenital anomalies or missing or late admission temperature recordings. The study included 288 neonates whose mean gestational age was 34.6±3.4 weeks, and their mean birth weight was 2.35±0.9 kg. Two-thirds (66%) of the neonates had core temperatures indicating hypothermia (axillary temperature of less than 36.5°C), one-third (33%) were normothermic, and only three (1%) were hyperthermic. Neonates with hypothermia had statistically lower gestational age, higher frequency of multiple births, prolonged need for respiratory support, higher rates of pulmonary hemorrhage, sepsis, intraventricular hemorrhage (IVH), and necrotizing enterocolitis, longer hospital stay, and mortality. CONCLUSIONS: There is a high incidence of neonatal hypothermia at NICU admission. Lower gestational age, increased multiples, lower APGAR score, lower birth weight, and lack of antenatal steroids were significantly associated with hypothermia at NICU admission. Hypothermia was found to be a significant factor contributing to increased mortality and morbidity rates in affected neonates.


Subject(s)
Hypothermia , Infant, Premature , Humans , Infant, Newborn , Birth Weight , Hemorrhage , Hypothermia/epidemiology , Infant Mortality , Intensive Care Units, Neonatal , Morbidity
3.
R Soc Open Sci ; 10(9): 230634, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37771961

ABSTRACT

Recent outbreaks of Mpox and Ebola, and worrying waves of COVID-19, influenza and respiratory syncytial virus, have all led to a sharp increase in the use of epidemiological models to estimate key epidemiological parameters. The feasibility of this estimation task is known as the practical identifiability (PI) problem. Here, we investigate the PI of eight commonly reported statistics of the classic susceptible-infectious-recovered model using a new measure that shows how much a researcher can expect to learn in a model-based Bayesian analysis of prevalence data. Our findings show that the basic reproductive number and final outbreak size are often poorly identified, with learning exceeding that of individual model parameters only in the early stages of an outbreak. The peak intensity, peak timing and initial growth rate are better identified, being in expectation over 20 times more probable having seen the data by the time the underlying outbreak peaks. We then test PI for a variety of true parameter combinations and find that PI is especially problematic in slow-growing or less-severe outbreaks. These results add to the growing body of literature questioning the reliability of inferences from epidemiological models when limited data are available.

4.
BMC Glob Public Health ; 1(1): 28, 2023.
Article in English | MEDLINE | ID: mdl-38798822

ABSTRACT

Background: Controlling the spread of infectious diseases-even when safe, transmission-blocking vaccines are available-may require the effective use of non-pharmaceutical interventions (NPIs), e.g., mask wearing, testing, limits on group sizes, venue closure. During the SARS-CoV-2 pandemic, many countries implemented NPIs inconsistently in space and time. This inconsistency was especially pronounced for policies in the United States of America (US) related to venue closure. Methods: Here, we investigate the impact of inconsistent policies associated with venue closure using mathematical modeling and high-resolution human mobility, Google search, and county-level SARS-CoV-2 incidence data from the USA. Specifically, we look at high-resolution location data and perform a US-county-level analysis of nearly 8 million SARS-CoV-2 cases and 150 million location visits, including 120 million church visitors across 184,677 churches, 14 million grocery visitors across 7662 grocery stores, and 13.5 million gym visitors across 5483 gyms. Results: Analyzing the interaction between venue closure and changing mobility using a mathematical model shows that, across a broad range of model parameters, inconsistent or partial closure can be worse in terms of disease transmission as compared to scenarios with no closures at all. Importantly, changes in mobility patterns due to epidemic control measures can lead to increase in the future number of cases. In the most severe cases, individuals traveling to neighboring jurisdictions with different closure policies can result in an outbreak that would otherwise have been contained. To motivate our mathematical models, we turn to mobility data and find that while stay-at-home orders and closures decreased contacts in most areas of the USA, some specific activities and venues saw an increase in attendance and an increase in the distance visitors traveled to attend. We support this finding using search query data, which clearly shows a shift in information seeking behavior concurrent with the changing mobility patterns. Conclusions: While coarse-grained observations are not sufficient to validate our models, taken together, they highlight the potential unintended consequences of inconsistent epidemic control policies related to venue closure and stress the importance of balancing the societal needs of a population with the risk of an outbreak growing into a large epidemic. Supplementary Information: The online version contains supplementary material available at 10.1186/s44263-023-00028-z.

5.
PLoS Negl Trop Dis ; 16(6): e0010436, 2022 06.
Article in English | MEDLINE | ID: mdl-35653307

ABSTRACT

Widespread application of insecticide remains the primary form of control for Chagas disease in Central America, despite only temporarily reducing domestic levels of the endemic vector Triatoma dimidiata and having little long-term impact. Recently, an approach emphasizing community feedback and housing improvements has been shown to yield lasting results. However, the additional resources and personnel required by such an intervention likely hinders its widespread adoption. One solution to this problem would be to target only a subset of houses in a community while still eliminating enough infestations to interrupt disease transfer. Here we develop a sequential sampling framework that adapts to information specific to a community as more houses are visited, thereby allowing us to efficiently find homes with domiciliary vectors while minimizing sampling bias. The method fits Bayesian geostatistical models to make spatially informed predictions, while gradually transitioning from prioritizing houses based on prediction uncertainty to targeting houses with a high risk of infestation. A key feature of the method is the use of a single exploration parameter, α, to control the rate of transition between these two design targets. In a simulation study using empirical data from five villages in southeastern Guatemala, we test our method using a range of values for α, and find it can consistently select fewer homes than random sampling, while still bringing the village infestation rate below a given threshold. We further find that when additional socioeconomic information is available, much larger savings are possible, but that meeting the target infestation rate is less consistent, particularly among the less exploratory strategies. Our results suggest new options for implementing long-term T. dimidiata control.


Subject(s)
Chagas Disease , Insecticides , Triatoma , Animals , Bayes Theorem , Chagas Disease/epidemiology , Chagas Disease/prevention & control , Disease Vectors
6.
Ann Burns Fire Disasters ; 35(4): 278-299, 2022 Dec.
Article in English | MEDLINE | ID: mdl-38680625

ABSTRACT

Fire-related burns contribute significantly to the global burden of burn injury and mortality. Alcohol and/or drug intoxication poses a risk to burn and fire-related injury, whether intentional or unintentional, but such evidence is scarce in the African context. This review aimed to fill the knowledge gap on health determinants of fire-related morbidity and mortality regionally by investigating the role of alcohol and drug intoxication in such events. Using key concepts, an extensive search was performed on 25 databases for relevant publications. Eligible articles were critically appraised using the appraisal tool for cross-sectional studies (AXIS tool), adapted to the review's objectives and outcomes. A total of 42 articles were included, of which less than half were solely investigating burn/fire-related events. Others indirectly mentioned burn injuries as part of larger health burdens such as injury, trauma, violence and other diseases. The measurement of alcohol and/or drug intoxication was inconsistent between studies with varying results. Alcohol and drug impairment in burn incidents in Africa requires evidence-based epidemiological research, and this review illustrated the limited scope of this topic in current literature. Routine toxicological results from post-mortem examinations were identified as important data sources and several research recommendations were provided.


Les atteintes lors d'un incendie représentent une partie non négligeable de l'ensemble des brûlures. Qu'elle soit intentionnelle ou non, l'intoxication alcoolique et/ou par stupéfiant en augmente le risque. Mais les données à ce sujet sont rares en Afrique. Nous avons effectué une revue systématique sur 25 banques de données. Les 42 articles sélectionnés, dont moins de la moitié exploraient les brûlures lors d'un incendie (les autres comprenaient les brûlures dans un cadre traumatique plus général- blessure, traumatisme, violence, etc.), ont été étudiés selon la méthode AXIS. La mesure de l'alcoolémie et les recherches de toxiques étaient variablement reprises dans les articles, le diagnostic d'intoxication reposant essentiellement sur la clinique en Afrique et il y a donc peu de données basées sur des chiffres, les plus fréquentes étant celles provenant de prélèvements autopsiques. Il s'agit donc d'améliorer le diagnostic de ces intoxications en cas de brûlure lors d'un incendie.

7.
J Genet Eng Biotechnol ; 16(2): 295-304, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30733738

ABSTRACT

Proteases are the hydrolytic enzymes which hydrolyzes peptide bond between proteins with paramount applications in pharmaceutical and industrial sector. Therefore production of proteases with efficient characteristics of biotechnological interest from novel strain is significant. Hence, in this study, an alkaline serine protease produced by Bacillus cereus strain S8 (MTCC NO 11901) was purified and characterized. The alkaline protease was purified by ammonium sulfate precipitation (50%), ion exchange (DEAE-Cellulose) and gel filtration (Sephadex G-100) chromatographic techniques. As a result of this purification, a protein with specific activity of 300U/mg protein was obtained with purification fold 17.04 and recovery percentage of 34.6%. The molecular weight of the purified protease was determined using SDS-PAGE under non-reducing (71 kDa) and reducing conditions (35 kDa and 22 kDa). Zymogram analysis revealed that proteolytic activity was only associated with 22 kDa. These results indicate that existence of the enzyme as dimer in its native state. The molecular weight of the protease (22 kDa) was also determined by gel filtration (Sephadex G-200) chromatography and it was calculated as 21.8 kDa. The optimum activity of the protease was observed at pH 10.0 and temperature 70 °C with great stability towards pH and temperature with casein as a specific substrate. The enzyme was completely inhibited by PMSF and TLCK indicating that it is a serine protease of trypsin type. The enzyme exhibits a great stability towards organic solvents, oxidizing and bleaching agents and it is negatively influenced by Li2+ and Co2+ metal ions. The purified protein was further characterized by Matrix Assisted Laser Desorption Ionization/Mass Spectroscopy (MALDI/MS) analysis which reveals that total number of amino acids is 208 with isoelectric point 9.52.

8.
Toxicon ; 93: 20-3, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25447769

ABSTRACT

Envenoming by colubrid snakes is rarely reported. However, some colubrid snakes (e.g. Rhabdophis tigrinus and Rhabdophis subminiatus) have caused severe systemic envenoming. We report here the first case of a bite with systemic envenoming by Balanophis ceylonensis, an opisthoglyphous natricine colubrid, in Sri Lanka. A 33-year-old healthy male field biologist was bitten while handling the snake for photography. Within 5 min of the bite on the dorsum of the right hand, he reported severe occipital headache, photophobia, chills and transient loss of consciousness. He vomited blood-stained gastric contents and bled from venepuncture sites. He had a markedly elevated INR and positive D-dimer test suggestive of significant coagulopathy that was treated with infusions of fresh frozen plasma. He recovered and left hospital after 96 h and subsequent investigations, including electroencephalogram, were normal. We conclude that B. ceylonensis should be regarded as a medically significant venomous snake. This case highlights the need for further studies of the oral secretions (venoms) of colubrid snakes.


Subject(s)
Blood Coagulation Disorders/pathology , Colubridae , Headache/pathology , Photophobia/pathology , Snake Bites/epidemiology , Snake Bites/pathology , Adult , Animals , Blood Coagulation Disorders/etiology , Fibrin Fibrinogen Degradation Products/metabolism , Headache/etiology , Humans , International Normalized Ratio , Male , Photophobia/etiology , Snake Bites/complications , Sri Lanka/epidemiology
9.
J Relig Health ; 54(2): 649-63, 2015 Apr.
Article in English | MEDLINE | ID: mdl-24944165

ABSTRACT

Religious/spiritual (r/s) characteristics of physicians influence their attitude toward integrative medicine and spiritual care. Indonesia physicians collaborate with traditional, complementary, and alternative medicine (TCAM) professionals within modern healthcare system, while Indian physicians are not reported to do so. The aim of the study was to understand the r/s characteristics and their influence on Indian and Indonesian physicians' acceptance of TCAM/spirituality in modern healthcare system. An exploratory, pilot, cross-cultural, cross-sectional study, using Religion and Spirituality in Medicine, and Physician Perspectives (RSMPP) survey questionnaire, compared r/s characteristics and perspectives on integrative medicine of 169 physicians from two allopathic, Sweekar-Osmania University (Sweekar-OU), India, University of Airlanga (UNAIR), Indonesia, and a TCAM/Central Research Institute of Unani Medicine (CRIUM) institute from India. More physicians from UNAIR and CRIUM (89.1 %) described themselves as "very"/"moderately" religious, compared to 63.5 % Sweekar-OU (p = 0.0000). Greater number of (84.6 %) UNAIR physicians described themselves as "very" spiritual and also significantly high (p < 0.05) in intrinsic religiosity as compared to Sweekar-OU and TCAM physicians; 38.6 % of UNAIR and 32.6 % of CRIUM participants reported life-changing spiritual experiences in clinical settings as against 19.7 % of Sweekar-OU; 92.3 % of UNAIR, compared to CRIUM (78.3 %) and Sweekar-OU (62 %), felt comfortable attending to patients' spiritual needs, (p = 0.0001). Clinical comfort and not r/s characteristics of participants was the significant (p = 0.05) variable in full regression models, predictive of primary outcome criteria; "TCAM or r/s healing as complementary to allopathic treatment." In conclusion, mainstreaming TCAM into healthcare system may be an initial step toward both integrative medicine and also improving r/s care interventions by allopathic physicians.


Subject(s)
Attitude of Health Personnel , Cross-Cultural Comparison , Integrative Medicine , Physicians/psychology , Religion and Medicine , Spirituality , Adult , Complementary Therapies/psychology , Cross-Sectional Studies , Female , Humans , India , Indonesia , Male , Physicians/statistics & numerical data , Pilot Projects , Surveys and Questionnaires
10.
Oral Oncol ; 50(5): 498-505, 2014 May.
Article in English | MEDLINE | ID: mdl-24613543

ABSTRACT

OBJECTIVE: Overexpression of epidermal growth factor receptor (EGFR) in many cancers makes it an attractive therapeutic target. This study evaluated the clinical utility of nimotuzumab, a monoclonal anti-EGFR antibody, used concurrently with radiotherapy (RT) and chemoradiotherapy (CRT) in squamous cell carcinoma of the head and neck (SCCHN). METHODS: This open-label study randomized 92 treatment-naïve patients (1:1) with advanced SCCHN into chemoradiation (CRT ± nimotuzumab) or radiation (RT ± nimotuzumab) group by investigator's discretion; these were further randomized into CRT + nimotuzumab or CRT and RT + nimotuzumab or RT groups, respectively. Treatment included 6 cycles each of cisplatin (50 mg/week), nimotuzumab (200 mg/week), and RT (total dose, 60-66 Gy). Response (tumor size reduction) was assessed at Month 6 post-treatment and survival, at Month 60. RESULTS: Forty and 36 patients in the chemoradiation and radiation groups, respectively (intent-to-treat population) were evaluated. Overall response at Month 6 post-treatment was 100% with CRT + nimotuzumab, 70% with CRT, 76% with RT + nimotuzumab, and 37% with RT. At Month 60, overall survival was 57% with CRT + nimotuzumab, 26% with CRT (P = 0.03), 39% with RT + nimotuzumab, and 26% with RT (P > 0.05). Median overall survival was not reached for CRT + nimotuzumab; it was 21.94 months for CRT (P = 0.0078), 14.36 months for RT + nimotuzumab, and 12.78 months for RT (P = 0.45). Risk of death was 64% lower with CRT + nimotuzumab than with CRT (95%CI: 0.37, 1.56), and 24% lower with RT + nimotuzumab than with RT (95%CI: 0.16, 0.79). Thus nimotuzumab was safe and well tolerated with few mild to moderate self-limiting adverse events. CONCLUSION: Concurrent use of nimotuzumab with CRT/RT is safe and provides long-term survival benefit.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Agents/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Head and Neck Neoplasms/drug therapy , Adult , Aged , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/radiotherapy , Combined Modality Therapy , ErbB Receptors/metabolism , Female , Head and Neck Neoplasms/metabolism , Head and Neck Neoplasms/radiotherapy , Humans , Male , Middle Aged , Survival Analysis
11.
J Relig Health ; 53(4): 1161-75, 2014 Aug.
Article in English | MEDLINE | ID: mdl-23625126

ABSTRACT

Allopathic medical professionals in developed nations have started to collaborate with traditional, complementary, and alternative medicine (TCAM) to enquire on the role of religion/spirituality (r/s) in patient care. There is scant evidence of such movement in the Indian medical community. We aim to understand the perspectives of Indian TCAM and allopathic professionals on the influence of r/s in health. Using RSMPP (Religion, Spirituality and Medicine, Physician Perspectives) questionnaire, a cross-sectional survey was conducted at seven (five TCAM and two allopathic) pre-selected tertiary care medical institutes in India. Findings of TCAM and allopathic groups were compared. Majority in both groups (75% of TCAM and 84.6% of allopathic practitioners) believed that patients' spiritual focus increases with illness. Up to 58% of TCAM and allopathic respondents report patients receiving support from their religious communities; 87% of TCAM and 73% of allopaths believed spiritual healing to be beneficial and complementary to allopathic medical care. Only 11% of allopaths, as against 40% of TCAM, had reportedly received 'formal' training in r/s. Both TCAM (81.8%) and allopathic (63.7%) professionals agree that spirituality as an academic subject merits inclusion in health education programs (p = 0.0003). Inclusion of spirituality in the health care system is a need for Indian medical professionals as well as their patients, and it could form the basis for integrating TCAM and allopathic medical systems in India.


Subject(s)
Attitude of Health Personnel , Complementary Therapies , Integrative Medicine/methods , Medicine, Traditional , Religion and Medicine , Spirituality , Adult , Cross-Sectional Studies , Female , Humans , India , Male , Middle Aged , Surveys and Questionnaires , Young Adult
12.
J Immunol Methods ; 394(1-2): 121-4, 2013 Aug 30.
Article in English | MEDLINE | ID: mdl-23707325

ABSTRACT

The development of vaccines against tuberculosis continues to be hindered by the lack of correlates of protection. Immunity to Mycobacterium tuberculosis (M.tb) infection relies predominantly on cell mediated response, which is routinely measured using a read-out of host cytokine profiles. However, to date none of the cytokine profiles have been found to predict protection. A number of functional in vitro approaches that measure growth of mycobacteria pre- and post-vaccination as a potential functional surrogate marker for vaccine take have been developed. The use of a reporter-gene tagged BCG-lux assay measuring the viability of mycobacteria in whole blood samples has previously been described by our group to assess vaccine immunogenicity. Since only very small blood samples are usually available in paediatric studies, we now report a modification of the BCG-lux assay to reduce the volume required and make it more field-friendly. Our results show that a 2-fold reduction in blood volume made no significant difference to bacterial growth ratios, used as the main read-out. These results confirm the suitability of the BCG-lux assay for functional studies of vaccine immunogenicity and immunopathogenesis in young children and could play a role in late-phase TB vaccine trials of novel candidates.


Subject(s)
BCG Vaccine/immunology , Microbiological Techniques/methods , Mycobacterium tuberculosis/growth & development , Adult , Humans , Infant
13.
J Nepal Health Res Counc ; 10(1): 61-5, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22929640

ABSTRACT

BACKGROUND: Isolated fractures of metacarpals and phalanges are the commonest injuries affected upper extremity, which constitute about 10% of skeletal fractures in general. Fifth metacarpal (boxer's fractures) being the most common. The objective of this study was to investigate the outcome of treatment of the displaced neck and sub-capital fractures of the fifth metacarpal by percutaneous K wire fixation. METHODS: An observational study was conducted in the department of orthopedics Patan hospital as an outpatient procedure from January 2010 to January 2012. All adult patients with unilateral fracture of neck of fifth metacarpal bone were included. Whose physis was open, having previous hand injury or diseases causing deformity or impaired hand function and when fracture was more than 7 days old, were excluded from the study. RESULTS: Twenty eight of 35 patients obtained anatomic reduction, and 7 patients had 2/3 apposition of bone end and no rotational deformity. Follow-up was available for only 30 patients. The follow-up time was up to 12 weeks. The head/shaft angle of the fifth metacarpal was 60.60 degrees ±9.39 degrees preoperatively, and 14.20 degrees ±7.32 degrees postoperatively, and 15.60 degrees ±6.95 degrees in 12 weeks postoperatively. The difference between preoperative and postoperative angles was highly significant. The range of motion of the metacarpal joint was 86.73 degrees ±6.13 degrees postoperatively, which was not significantly different compared with that of uninjured side which was 90.93 degrees ±3.18. The difference between preoperative and postoperative angles was highly significant. The range of motion of the metacarpal joint was not significantly different compared with that of uninjured side. The average union time was 5.46 weeks ±1.22. CONCLUSIONS: This method under consideration does not disturb the fracture site itself, the Kirschner wire being introduced in retrograde fashion makes it easier to correctly place the wire, which gives reasonably stable fixation, gives excellent results in a high proportion of selected cases. Local anesthesia is an added advantage.


Subject(s)
Bone Wires , Finger Phalanges/injuries , Fracture Fixation, Internal/methods , Fractures, Bone/surgery , Metacarpal Bones/injuries , Female , Humans , Male , Metacarpal Bones/surgery , Qualitative Research , Young Adult
14.
Int J Cancer ; 125(1): 91-103, 2009 Jul 01.
Article in English | MEDLINE | ID: mdl-19358280

ABSTRACT

Human papilloma virus is a causative factor in the etiology of cervical cancer with HPV16 being the most prevalent genotype associated with it. Intratype variations in oncogenic E6/E7 and capsid L1 proteins of HPV 16 besides being of phylogenetic importance, are associated with risk of viral persistence and progression. The objective of this multicentric study was to identify HPV-16 E6, E7 and L1 variants prevalent in India and their possible biological effects. Squamous cell cervical cancer biopsies were collected from 6 centres in India and examined for the presence of HPV 16. Variants of HPV-16 were characterized by full length sequence analysis of L1, E6 and E7 genes in 412 samples. Similar distribution of the variants was seen from the different centres/regions, with the European variant E350G being the most prevalent (58%), followed by American Asian variant (11.4%). Fifty six changes were seen in E6 region, 31 being nonsynonymous. The most frequent being L83V (72.3%), Q14H (13.1%) and H78Y (12.1%). Twenty-nine alterations were seen in E7 region, with 12 being nonsynonymous. The most frequent being F57V (9%). L1 region showed 204 changes, of which 67 were nonsynonymous. The most frequent being 448insS (100%), and 465delD (100%), H228D (94%), T292A (85%). The identified variants some new and some already reported can disrupt pentamer formation, transcriptional regulation of the virus, L1 protein interface interaction, B and T cell epitopes, p53 degradation, and thus their distribution is important for development of HPV diagnostics, vaccine, and for therapeutic purpose.


Subject(s)
Capsid Proteins/genetics , Genetic Variation , Human papillomavirus 16/genetics , Oncogene Proteins, Viral/genetics , Papillomavirus Infections/genetics , Repressor Proteins/genetics , Uterine Cervical Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/virology , Female , Human papillomavirus 16/classification , Humans , India , Middle Aged , Papillomavirus E7 Proteins , Papillomavirus Infections/epidemiology , Papillomavirus Infections/virology , Uterine Cervical Neoplasms/virology
15.
Gynecol Oncol ; 104(2): 352-61, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17098279

ABSTRACT

OBJECTIVES: Features of deregulated Notch1 signaling and NF-kappaB activation have independently been reported in cervical cancers. Here, we have extended these observations and examined both these pathways simultaneously in human cervical cancer tissue. Further, we have investigated the potential cross-talk between these pathways in a human cervical cancer derived cell line CaSki, which mirrors features of Notch activation as in the majority of human cervical cancers. METHODS: Cervical tissue samples were analyzed for the expression of Notch1, Jagged 1, Hes1, pAKT, NF-kappaB p50, NF-kappaB p65, IkappaB-alpha, Bcl-2, CyclinD1, Cdk9, c-Fos, and p53 by immunohistochemistry. A total of 352 samples were analyzed which included 69 normal cervical tissue, 132 preinvasive lesions and 151 squamous cell carcinomas of the uterine cervix. Dual immunofluorescent analysis was performed to evaluate the coexpression of Notch1 and NF-kappaB. Transcriptional reporter assays and xenografts were undertaken with CaSki cells. RESULTS: Features of Notch1 activation as measured by intracellular Notch1, high levels of Jagged1, Hes1 and Cdk9 were paralleled by nuclear translocation of both NF-kappaB p50 and p65 with target gene expression (IkappaB-alpha, Bcl-2, and CyclinD1) in human cervical cancer sections. Reporter assays in CaSki cells are consistent with Notch being an upstream regulator of NF-kappaB. Further, the xenografts recreate key aspects of human cancer tissue. CONCLUSIONS: Results from this study suggest that there is a co-activation of Notch1 and NF-kappaB signaling pathways at the cellular level in the majority of human cervical cancers, with Notch as an upstream regulator.


Subject(s)
Carcinoma, Squamous Cell/metabolism , NF-kappa B/biosynthesis , Receptor, Notch1/biosynthesis , Uterine Cervical Dysplasia/metabolism , Uterine Cervical Neoplasms/metabolism , Animals , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Cell Line, Tumor , Cell Nucleus/metabolism , Disease Progression , Female , Humans , Immunohistochemistry , Mice , Mice, Nude , NF-kappa B/genetics , NF-kappa B/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-fos/biosynthesis , Proto-Oncogene Proteins c-fos/genetics , Receptor, Notch1/genetics , Receptor, Notch1/metabolism , Signal Transduction , Transplantation, Heterologous , Tumor Suppressor Protein p53/biosynthesis , Tumor Suppressor Protein p53/genetics , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/pathology , Uterine Cervical Dysplasia/genetics , Uterine Cervical Dysplasia/pathology
17.
J Indian Med Assoc ; 101(1): 28-30, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12841504

ABSTRACT

A two and half years old male child of sinus histiocytosis with massive lymphadenopathy, paraplegia and spinal cord involvement was treated with surgery and radiotherapy for the spinal cord compression and later with chemotherapy for his nodal disease in the neck. There was a significant improvement in his neurologic status as well as in his nodal status reiterating the role of combination therapy in this disease.


Subject(s)
Histiocytosis, Sinus/pathology , Spinal Cord Compression/pathology , Child, Preschool , Histiocytosis, Sinus/therapy , Humans , Magnetic Resonance Imaging , Male , Spinal Cord Compression/surgery
18.
Ann Otol Rhinol Laryngol ; 111(1): 50-6, 2002 Jan.
Article in English | MEDLINE | ID: mdl-11803953

ABSTRACT

This prospective study, performed from 1991 to 1996, analyzes the differences in oncological safety, functional utility, and surgical morbidity in 14 advanced lesions of the larynx (10 T3 and 4 T4; 7 N+) and 40 pyriform sinus lesions (1 T2, 20T3, and 19 T4; 29 N+) subjected to Pearson near-total laryngectomy. The laryngeal cancer patients healed much faster, with a minimal wound complication rate of 28%, in comparison to the 68% rate encountered in the pyriform sinus cases (p < .05). The 3-year disease-free survival rate for the laryngeal cancers was 74%, while the 5-year survival rates for pyriform sinus cases were 66% for medial wall lesions and 54% for lateral wall lesions. Lung-powered shunt speech deemed qualitatively superior by acoustic analysis was obtained in 81% of the individuals (93% in laryngeal cases and 76% in pyriform sinus cases). Aspiration-free deglutition was achieved by 90% over periods ranging from 15 to 30 days. This study conclusively attests to the therapeutic efficacy of near-total laryngectomy for advanced lesions of the larynx and pyriform sinus that are unsuitable for radiotherapy, that are deemed too large or risky (because of aspiration) for partial laryngectomy, and that in the past would have merited total laryngectomy.


Subject(s)
Carcinoma, Squamous Cell/surgery , Laryngeal Neoplasms/surgery , Laryngectomy , Adult , Aged , Carcinoma, Squamous Cell/pathology , Female , Humans , Laryngeal Neoplasms/pathology , Laryngectomy/adverse effects , Laryngectomy/methods , Male , Middle Aged , Postoperative Complications , Prospective Studies , Speech , Speech, Esophageal
19.
Plant Cell Rep ; 10(12): 617-20, 1992 Jan.
Article in English | MEDLINE | ID: mdl-24212874

ABSTRACT

We describe here a liquid culture system for the regeneration of shoots at high frequencies from mature cotyledon tissues of three genotypes of sunflower (Helianthus annuus L.) one of which had previously been found to be recalcitrant to regeneration when cotyledons were cultured on solid medium. Cotyledons were excised from 2-day-old seedlings and incubated in liquid Murashige and Skoog's modified medium supplemented with 5.4 µM naphthaleneacetic acid (NAA) and 4.4 µM benzylaminopurine (BAP). After two weeks in culture, the whole upper surface of regenerating explants was covered with green shootlets. The percentages of regenerating explants of three genotypes varied between 60 and 70%, and the number of shoots per regenerating explant was highly increased. The shootlets were transferred to solid Murashige and Skoog's medium allowing shoot development, then to rooting medium. Rooted plantlets were successfully acclimatized and gave fertile plants. The role of liquid medium culture in the induction of sunflower regeneration is discussed.

20.
Plant Cell Rep ; 10(4): 204-7, 1991 Jul.
Article in English | MEDLINE | ID: mdl-24221547

ABSTRACT

The effects of CoCl2, AgNO3 and ethylene released by exogenous 2-chloroethylphosphonic acid (Ethephon), were studied on shoot regeneration from cotyledons of Helianthus annuus cv. E8206R, a poorly regenerative cultivar. Inhibition of ethylene biosynthesis by CoCl2, at concentrations of 20 µK, provoked a substantial enhancement of shoot regeneration (30 %): the control was poorly regenerative. However, CoCl2 had no effect when Ethephon was supplied. Inhibition of ethylene action by AgNO3, at concentrations of 10-25 µM, caused a significant increase in plant regeneration: 25 % instead of 1.2 % in the control. Furthermore, addition of Ethephon to AgNO3-treated tissues failed to reduce the stimulation of shoot regeneration caused by AgNO3. On the basis of these findings, it is suggested that ethylene inhibits the regeneration process from cotyledons of sunflower.

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