The effect of differential force system and minimal surgical intervention on orthodontic tooth movement and root resorption.

OBJECTIVE: The primary objective of this study was to quantify the orthodontic tooth movement (OTM) and orthodontically induced root resorption (OIRR) with differential force system in conjunction with minimal surgical insult. MATERIAL AND METHODS: 15-week-old, 48 male Wistar rats were used in the research and were randomly divided into six groups: 1. Group 1 (8 Wistar rats): OTM for 14 days with 8-g force; 2. Group 2 (8 Wistar rats): OTM for 14 days with 25-g force; 3. Group 3 (8 Wistar rats): OTM for 14 days with 100-g force; 4. Group 4 (8 Wistar rats): OTM for 14 days with 8-g force and alveolar decortications (ADs); 5. Group 5 (8 Wistar rats): OTM for 14 days with 25-g force and ADs; 6. Group 6 (8 Wistar rats): OTM for 14 days with 100-g force and ADs. A nickel-titanium spring was used to protract the molar mesially using maxillary incisors as an anchorage. ADs (minimal surgical insult) were done using a hand piece and a round bur, adjacent to the left first maxillary molar on the palatal alveolar bone. After 14 days of OTM, Wistar rats were killed and microfocus computed tomography and histological analysis were performed. RESULTS: The 100-g group showed significant increase (P < 0.05) in OTM. However, with ADs, the OTM was significantly higher (P < 0.05) in 8 and 100 g. In addition, with ADs, there is significant increase (P < 0.05) in OIRR and significant decrease (P < 0.05) in bone volume fraction. Histological quantification of tartrate-resistant acid phosphatase indicated a significant increase (P < 0.05) in the number of osteoclasts with ADs when compared without ADs. CONCLUSIONS: Light force in conjunction with ADs are optimal to accelerate the OTM. Additionally, ADs increases the OIRR.

A need for a health IT portal to disseminate information about national health programmes in India.

The objective of our study is to evaluate information about the national health programmes in India, available over the internet and to study the challenges faced while acquiring this information. To achieve our objective, we used the key words national health programmes OR public health programmes OR health programs AND India in Google from January 1-January 10 2012, to find information about the existing health programmes. We chose first 20 web links across all the three search terms to yield 60 websites, which were then reviewed for their relevance. Only 16 websites were found to be relevant that met the inclusion criteria. The study showed that there was inadequate information about the existing national health programmes in India. This suggests a need to develop a national public health IT portal that can disseminate information about the various health programmes in a more structured manner and which is tailored to the needs of diverse group of stakeholders.

A case for pharmacogenomics in management of cardiac arrhythmias.

Disorders of the cardiac rhythm are quite prevalent in clinical practice. Though the variability in drug response between individuals has been extensively studied, this information has not been widely used in clinical practice. Rapid advances in the field of pharmacogenomics have provided us with crucial insights on inter-individual genetic variability and its impact on drug metabolism and action. Technologies for faster and cheaper genetic testing and even personal genome sequencing would enable clinicians to optimize prescription based on the genetic makeup of the individual, which would open up new avenues in the area of personalized medicine. We have systematically looked at literature evidence on pharmacogenomics markers for anti-arrhythmic agents from the OpenPGx consortium collection and reason the applicability of genetics in the management of arrhythmia. We also discuss potential issues that need to be resolved before personalized pharmacogenomics becomes a reality in regular clinical practice.

A dermoscopy survey to assess who is using it and why it is or is not being used.

BACKGROUND: Dermoscopy is a noninvasive method of evaluation of the colors and microstructures of the epidermis, dermo-epidermal junction, and papillary dermis not visible to the naked eye. These structures are correlated with histologic features and used to assess whether a lesion is benign or malignant, further indicating whether or not the lesion should be biopsied. OBJECTIVE: To obtain a better understanding of how many dermatologists are utilizing dermoscopy and their reasons for doing or not doing so. METHOD: A survey was conducted focusing on the prevalence of the use of dermoscopy by US dermatologists, the method by which they learned dermoscopy, how often they use or do not use it, and whether or not they feel it is effective. The survey was distributed to dermatologists attending a dermoscopy seminar at the American Academy of Dermatology's (AAD's) Summer Academy Meeting in 2007, as well as to dermatologists who expressed an interest in dermoscopy. E-mail addresses were also obtained from dermatologists who attended the AAD's Summer Academy Meeting, and subsequent surveys were e-mailed to them as a secondary means of obtaining the data. The survey was conducted online through a website: http://www.surveymonkey.com. One hundred and five dermatologists started the survey and ninety-seven finished it, a completion percentage of 92.4%. RESULTS: Of the 105 dermatologists who began the survey, the majority (63; 60%) had training or experience in dermoscopy, and 42 (40%) did not. Of the 63 individuals who responded positively to having training or experience in dermoscopy, the majority (41; 69.5%) learned dermoscopy through attendance of a seminar; reading a book and spending time with an experienced dermatologist were the second most popular methods of learning dermoscopy. The frequency of dermoscopy was evaluated, and it was found that 44 (42.7%) dermatologists used dermoscopy more than once daily, but 44 (42.7%) dermatologists reported never having used dermoscopy. Further information was obtained with regard to whether or not published algorithms were used by dermatologists to diagnose pigmented lesions. Pattern analysis was the most common algorithm used by 51 (89.5%) dermatologists questioned. The dermatologists were also questioned as to why they thought dermoscopy was effective or ineffective. The majority of dermatologists (32; 61.5%) believed that it was effective because it reduced patient anxiety. Helping to detect melanoma early was the second most popular reason for believing dermoscopy to be effective. Twenty-three (62.2%) dermatologists thought dermoscopy was ineffective as it was not more useful for detecting melanoma earlier than traditional methods. Eleven (29.7%) dermatologists said that they thought that dermoscopy took too long, which made it ineffective. To build on this, an additional question was asked: how long does dermoscopy take? The overwhelming response of dermatologists (52; 82.5%) was that dermoscopy took less than 1 min to evaluate one lesion. CONCLUSION: Dermoscopy is a widely used tool for the diagnosis of pigmented skin lesions. The use of dermoscopy is increasing in popularity amongst dermatologists, making it necessary to better understand dermoscopy and to analyse why physicians use it or do not use it. The survey indicated that the majority of physicians used dermoscopy in order to reduce patient anxiety and to detect melanoma early. The main reason why dermatologists found dermoscopy to be ineffective was that they felt that it was not useful in detecting melanoma earlier than traditional methods; 35% of dermatologists surveyed believed that dermoscopy required excessive training. These results imply that current training methods need to be modified. Training is limited to large dermatology centers and is not being transferred to general centers, which would allow it to be more accessible to a larger group of dermatologists in training. There is also a need to make the learning of dermoscopy easier and to establish a universal method of teaching. Overall, there is a need for improvement in the education of dermoscopy, ranging from training to information on the basics of dermoscopy. This would include aspects such as how long the average examination takes and dermoscopy's effectiveness compared with alternate methods.

Age dependence of adenovirus-specific neutralizing antibody titers in individuals from sub-Saharan Africa.

We assessed neutralizing antibody titers to adenovirus serotype 5 (Ad5) and six rare adenovirus serotypes, serotypes 11, 35, 50, 26, 48, and 49, in pediatric populations in sub-Saharan Africa. We observed a clear age dependence of Ad5-specific neutralizing antibody titers. These data will help to guide the development of Ad vector-based vaccines for human immunodeficiency virus type 1 and other pathogens.

Modulation of DNA vaccine-elicited CD8+ T-lymphocyte epitope immunodominance hierarchies.

Generating broad cellular immune responses against a diversity of viral epitopes is a major goal of current vaccine strategies for human immunodeficiency virus type 1 (HIV-1) and other pathogens. Virus-specific CD8(+) T-lymphocyte responses, however, are often highly focused on a very limited number of immunodominant epitopes. For an HIV-1 vaccine, the breadth of CD8(+) T-lymphocyte responses may prove to be critical as a result of the need to cover a wide diversity of viral isolates in the population and to limit viral escape from dominant epitope-specific T lymphocytes. Here we show that epitope modification strategies can alter CD8(+) T-lymphocyte epitope immunodominance hierarchies elicited by a DNA vaccine in mice. Mice immunized with a DNA vaccine expressing simian immunodeficiency virus Gag lacking the dominant D(b)-restricted AL11 epitope generated a marked and durable augmentation of responses specific for the subdominant D(b)-restricted KV9 epitope. Moreover, anatomic separation strategies and heterologous prime-boost regimens generated codominant responses against both epitopes. These data demonstrate that dominant epitopes can dramatically suppress the immunogenicity of subdominant epitopes in the context of gene-based vaccines and that epitope modification strategies can be utilized to enhance responses to subdominant epitopes.

Hexon-chimaeric adenovirus serotype 5 vectors circumvent pre-existing anti-vector immunity.

A common viral immune evasion strategy involves mutating viral surface proteins in order to evade host neutralizing antibodies. Such immune evasion tactics have not previously been intentionally applied to the development of novel viral gene delivery vectors that overcome the critical problem of anti-vector immunity. Recombinant, replication-incompetent adenovirus serotype 5 (rAd5) vector-based vaccines for human immunodeficiency virus type 1 and other pathogens have proved highly immunogenic in preclinical studies but will probably be limited by the high prevalence of pre-existing anti-Ad5 immunity in human populations, particularly in the developing world. Here we show that rAd5 vectors can be engineered to circumvent anti-Ad5 immunity. We constructed novel chimaeric rAd5 vectors in which the seven short hypervariable regions (HVRs) on the surface of the Ad5 hexon protein were replaced with the corresponding HVRs from the rare adenovirus serotype Ad48. These HVR-chimaeric rAd5 vectors were produced at high titres and were stable through serial passages in vitro. HVR-chimaeric rAd5 vectors expressing simian immunodeficiency virus Gag proved comparably immunogenic to parental rAd5 vectors in naive mice and rhesus monkeys. In the presence of high levels of pre-existing anti-Ad5 immunity, the immunogenicity of HVR-chimaeric rAd5 vectors was not detectably suppressed, whereas the immunogenicity of parental rAd5 vectors was abrogated. These data demonstrate that functionally relevant Ad5-specific neutralizing antibodies are focused on epitopes located within the hexon HVRs. Moreover, these studies show that recombinant viral vectors can be engineered to circumvent pre-existing anti-vector immunity by removing key neutralizing epitopes on the surface of viral capsid proteins. Such chimaeric viral vectors may have important practical implications for vaccination and gene therapy.

Immunogenicity of recombinant fiber-chimeric adenovirus serotype 35 vector-based vaccines in mice and rhesus monkeys.

Preexisting immunity to adenovirus serotype 5 (Ad5) has been shown to suppress the immunogenicity of recombinant Ad5 (rAd5) vector-based vaccines for human immunodeficiency virus type 1 (HIV-1) in both preclinical studies and clinical trials. A potential solution to this problem is to utilize rAd vectors derived from rare Ad serotypes, such as Ad35. However, rAd35 vectors have appeared less immunogenic than rAd5 vectors in preclinical studies to date. In this study, we explore the hypothesis that the differences in immunogenicity between rAd5 and rAd35 vectors may be due in part to differences between the fiber proteins of these viruses. We constructed capsid chimeric rAd35 vectors containing the Ad5 fiber knob (rAd35k5) and compared the immunogenicities of rAd5, rAd35k5, and rAd35 vectors expressing simian immunodeficiency virus Gag and HIV-1 Env in mice and rhesus monkeys. In vitro studies demonstrated that rAd35k5 vectors utilized the Ad5 receptor CAR rather than the Ad35 receptor CD46. In vivo studies showed that rAd35k5 vectors were more immunogenic than rAd35 vectors in both mice and rhesus monkeys. These data suggest that the Ad5 fiber knob contributes substantially to the immunogenicity of rAd vectors. Moreover, these studies demonstrate that capsid chimeric rAd vectors can be constructed to combine beneficial immunologic and serologic properties of different Ad serotypes.

Immunogenicity of heterologous prime-boost regimens involving recombinant adenovirus serotype 11 (Ad11) and Ad35 vaccine vectors in the presence of anti-ad5 immunity.

The high prevalence of preexisting immunity to adenovirus serotype 5 (Ad5) in human populations will likely limit the immunogenicity and clinical utility of recombinant Ad5 (rAd5) vector-based vaccines for human immunodeficiency virus type 1 and other pathogens. A potential solution to this problem is to utilize rAd vaccine vectors derived from rare Ad serotypes such as Ad35 and Ad11. We have previously reported that rAd35 vectors were immunogenic in the presence of anti-Ad5 immunity, but the immunogenicity of heterologous rAd prime-boost regimens and the extent that cross-reactive anti-vector immunity may limit this approach have not been fully explored. Here we assess the immunogenicity of heterologous vaccine regimens involving rAd5, rAd35, and novel rAd11 vectors expressing simian immunodeficiency virus Gag in mice both with and without anti-Ad5 immunity. Heterologous rAd prime-boost regimens proved significantly more immunogenic than homologous regimens, as expected. Importantly, all regimens that included rAd5 were markedly suppressed by anti-Ad5 immunity. In contrast, rAd35-rAd11 and rAd11-rAd35 regimens elicited high-frequency immune responses both in the presence and in the absence of anti-Ad5 immunity, although we also detected clear cross-reactive Ad35/Ad11-specific humoral and cellular immune responses. Nevertheless, these data suggest the potential utility of heterologous rAd prime-boost vaccine regimens using vectors derived from rare human Ad serotypes.