Human papillomavirus testing versus cytology in primary cervical cancer screening: End‐of‐study and extended follow‐up results from the Canadian cervical cancer screening trial

The Canadian Cervical Cancer Screening Trial was a randomized controlled trial comparing the performance of human papillomavirus (HPV) testing and Papanicolaou cytology to detect cervical intraepithelial neoplasia of grades 2 or worse (CIN2+) among women aged 30–69 years attending routine cervical cancer screening in Montreal and St. John's, Canada (n = 10,154). We examined screening and prognostic values of enrollment cytologic and HPV testing results. Extended follow‐up data were available for St. John's participants (n = 5,754; 501,682.6 person‐months). HPV testing detected more CIN2+ than cytology during protocol‐defined (82.9 vs. 44.4%) and extended (54.2 vs. 19.3%) follow‐up periods, respectively. Three‐year risks ranged from 0.87% (95% CI: 0.37–2.05) for HPV‐/Pap‐ women to 35.77% (95% CI: 25.88–48.04) for HPV+/Pap+ women. Genotype‐specific risks ranged from 0.90% (95% CI: 0.40–2.01) to 43.84% (95% CI: 32.42–57.24) among HPV? and HPV16+ women, respectively, exceeding those associated with Pap+ or HPV+ results taken individually or jointly. Ten‐year risks ranged from 1.15% (95% CI: 0.60–2.19) for HPV?/Pap? women to 26.05% (95% CI: 15.34–42.13) for HPV+/Pap+ women and genotype‐specific risks ranged from 1.13% (95% CI: 0.59–2.14) to 32.78% (95% CI: 21.15–48.51) among women testing HPV? and HPV16+, respectively. Abnormal cytology stratified risks most meaningfully for HPV+ women. Primary HPV testing every 3 years provided a similar or greater level of reassurance against disease risks as currently recommended screening strategies. HPV‐based cervical screening may allow for greater disease detection than cytology‐based screening and permit safe extensions of screening intervals; genotype‐specific testing could provide further improvement in the positive predictive value of such screening.     

Expression of apoptotic, cell proliferation regulatory, and structural proteins in actinic keratosis and their association with dermal elastosis

BACKGROUND: Actinic keratosis (AK) is a premalignant lesion caused by ultraviolet (UV) radiation and characterized by epithelial and connective tissue alterations. However, little is known about the link between connective and UV-damaged epithelial tissues in AK. OBJECTIVE AND METHODS: To examine the potential relationship between connective tissue degeneration and molecular alterations in epithelial cells without evident morphologic changes, 30 cases of AK (8, grade I; 10, grade II; 12, grade III), divided into three grades according to the proportion of dermal elastosis (in grade I, up to 30% of collagen degeneration; in grade II, 30-60%; in grade III, more than 60%), were immunohistochemically analyzed for the expression of Ki67, p53, p63, bcl-2, E-cadherin, 34-betaE12, and CD99. RESULTS: The increase in the solar elastosis grade was associated with an increase in positive cell numbers for all analyzed markers. Basal expression predominated in the lesions with low and moderate levels of connective tissue degeneration, while a basal and suprabasal expression pattern was prevalent in the lesions with high degeneration. In grade I and II lesions, proliferation marker, Ki67, expression was found to be significantly associated with the proapoptotic marker p53, while in grade III lesions, its expression was correlated with the anti-apoptotic marker, bcl-2. CONCLUSIONS: These results demonstrate that the epithelial expression of apoptotic, cell proliferation, and structural proteins is augmented with the increase of the solar elastosis grade. Thus, the grade of solar elastosis could be a helpful morphologic marker in the assessment of neoplastic changes in sun-damaged skin.     

Risk of lung cancer following exposure to carbon black, titanium dioxide and talc: results from two case-control studies in Montreal

The International Agency for Research on Cancer (IARC) recently evaluated the carcinogenicity of three poorly soluble weakly-toxic substances: carbon black, titanium dioxide and talc. Though there is evidence of carcinogenity in experimental animals for these substances, the evidence in humans is sparse and equivocal. In the context of two large population based case-control studies of lung cancer carried out in Montreal, we were able to study the possible relationships between the exposure to each of these substances and subsequent risk of lung cancer. We were able to distinguish talc used for industrial purposes from that used for cosmetic purposes. Interviews for Study I were conducted in 1979-1986 (857 cases, 533 population controls, 1,349 cancer controls) and interviews for Study II were conducted in 1996-2001 (1,236 cases and 1,512 controls). Detailed lifetime job histories were elicited, and a team of hygienists and chemists evaluated the evidence of exposure to a host of occupational substances. Lung cancer risk was analysed in relation to each exposure, adjusting for several potential confounders, including smoking. Subjects with occupational exposure to carbon black, titanium dioxide, industrial talc and cosmetic talc did not experience any detectable excess risk of lung cancer. The results are consistent with the recent evaluations of the IARC Monographs.     

Universal Mindfulness Training in Schools for Adolescents: a Scoping Review and Conceptual Model of Moderators,Mediators, and Implementation Factors

Prevention Science - There is evidence that universal school-based mindfulness training (SBMT) can have positive effects for young people. However, it is unknown who benefits most from such...     

Pain control after primary total knee replacement. A prospective randomised controlled trial of local infiltration versus single shot femoral nerve block

BackgroundWe report a prospective blinded randomised trial of local infiltration versus femoral nerve block in patients undergoing primary total knee replacement (TKR), in accordance with the CONSORT statement 2010.MethodsFifty patients in a teaching hospital were consented for the study. The study arms were intraoperative local anaesthesia (150 ml 0.2% ropivacaine/1 ml 1:1000 adrenaline/30 mg ketolorac) and femoral nerve block (30 ml 0.2% ropivacaine) with a primary outcome of pain score at 4 h post operatively. Secondary outcomes were pain at 2 h, pain scores before and after physiotherapy on day one, total opiate administered, time to physiotherapy goals and length of stay. Randomisation was by sealed envelope. The assessor was blinded and the patients partially blinded to the intervention.ResultsTen patients were excluded, eight before randomisation. The trial is complete. Forty patients were analysed for the primary outcome measure. The local infiltration group had significantly lower pain scores at 4 h post-operatively; mean [SD] score 2.1 [2.6] versus 6.8 [3.2], p < 0.00001 and on post-operative day one prior to physiotherapy; mean score 2.4 [2.3] versus 4.4 [2.3], p < 0.05. Total opiate use was also significantly lower in the local infiltration group; mean total 115 [50.3] mg versus 176.5 [103.5] mg, p < 0.01. There was no difference in any other outcome. There were no harms as a result of either intervention.ConclusionIntraoperative local infiltration gives superior pain relief compared to single shot femoral nerve block over the first 24 h following primary TKR and minimises post-operative opiate use.     

Characterization of Leishmania donovani antigens encapsulated in liposomes that induce protective immunity in BALB/c mice

Leishmania donovani promastigote membrane antigens (LAg) encapsulated in positively charged liposomes have been found to induce very significant levels of protection against experimental visceral leishmaniasis. The protectively immunized animals exhibited profound delayed-type hypersensitivity and antibody responses. The extent of protection induced by the same antigens, however, varied depending on the charge of the vesicles, with maximum induction by positively charged liposomes, followed by neutral liposomes and last negatively charged liposomes. Characterization of LAg and LAg entrapped in liposomes of different charges by Western blot analysis revealed the immunodominance of gp63 in all three vaccine preparations. The strong reactivity of antigens in a restricted antigen profile that included, in addition to gp63, 72-, 52-, 48-, 45-, 39-, and 20-kDa components in neutral and positively charged liposomes contrasted with the reactivity of a greater number of LAg components in negatively charged liposomes. Resistance to visceral leishmaniasis appears to depend on the immunity induced by gp63 and a few select antigens in association with the right liposomes. A striking similarity between the immunogenic profile of partially purified soluble antigens and that of LAg in neutral and positively charged liposomes suggests the potentiality of these antigens in future vaccine studies of L. donovani.     

Characterization of immunoglobulin G and its subclass response to Indian kala-azar infection before and after chemotherapy

Serologic parameters of kala-azar were evaluated by Western blot analysis. Sera from kala-azar patients with confirmed diagnoses were screened for immunoglobulin G (IgG) and IgG subclass-specific reactivity against Leishmania donovani membrane antigen (LAg). Heterogeneous LAg-specific IgG reactivity with numerous proteins with molecular masses ranging from 18 to 190 kDa was observed. Though the individual band patterns were varied, seven polypeptides of approximately 31, 34, 51, 63, 72, 91, and 120 kDa were immunoreactive with all the sera tested from kala-azar patients. The band patterns of the immunoblots of sera from patients after treatment and clinical cure with sodium antimony gluconate revealed a decrease in the frequency of the bands. Still, recognition of the 63- and 120-kDa bands was 100%, and the 55- and 91-kDa fractions were recognized in 93% of the sera from cured individuals. Among the IgG subclasses, IgG1 reacted with the greatest number of polypeptides. The 63-kDa protein was again detected by all of the IgG subclasses of all the sera tested. Other fractions recognized by the subclasses of more than 70% of the serum samples included those of 47, 51, 55, and 78 kDa. Following treatment, 63- and 51-kDa bands were the most reactive with the IgG subclasses. LAg-associated cross-reaction with other reference human antisera revealed a mild reactivity of the 63-kDa polypeptide with some of the serum samples from leprosy, malaria, typhoid, tuberculosis, and healthy controls. Western blot analysis of LAg entrapped in liposomes, strong vaccine candidates against experimental visceral leishmaniasis, revealed a more restricted band pattern. The 63-kDa fraction revealed by all pre- and posttreatment sera showed almost negligible levels of cross-reaction with sera from patients with other diseases or from healthy controls. These observations provide insight into induced immunity during kala-azar infection for future application.     

Strategies of enhancing bone regenerate formation in distraction osteogenesis

Distraction osteogenesis (DO) is a commonly used technique in multiple orthopedic sub-specialties, including trauma, oncology and pediatrics. This technique aims to produce new bone formation in the distraction gap in a controlled manner. The issue with this technique has been the high risk of complications, one of which is poor regenerate formation during the distraction process. Although several factors (including patient and operative factors) and techniques (including surgical, mechanical and pharmacological) have been described to ensure successful regenerate formation during the process of DO, these factors are sometimes difficult to control clinically. Our aim from this review is to highlight the different factors that affect DO, modalities to assess the regenerate and review treatment options for poor regenerate in the distraction gap. In addition, we propose a management protocol derived from the available literature that can be used to facilitate the management of inadequate regenerate formation.