Photodynamic therapy of early stage oral cavity and oropharynx neoplasms: an outcome analysis of 170 patients

The indications of photodynamic therapy (PDT) of oral cavity and oropharynx neoplasms are not well defined. The main reason is that the success rates are not well established. The current paper analyzes our institutional experience of early stage oral cavity and oropharynx neoplasms (Tis-T2) to identify the success rates for each subgroup according to T stage, primary or non-primary treatment and subsites. In total, 170 patients with 226 lesions are treated with PDT. From these lesions, 95 are primary neoplasms, 131 were non-primaries (recurrences and multiple primaries). The overall response rate is 90.7% with a complete response rate of 70.8%. Subgroup analysis identified oral tongue, floor of mouth sites with more favorable outcome. PDT has more favorable results with certain subsites and with previously untreated lesions. However, PDT can find its place for treating lesions in previously treated areas with acceptable results

Alteration of proliferation and apoptotic markers in normal and premalignant tissue associated with prostate cancer

BACKGROUND: Molecular markers identifying alterations in proliferation and apoptotic pathways could be particularly important in characterizing high-risk normal or pre-neoplastic tissue. We evaluated the following markers: Ki67, Minichromosome Maintenance Protein-2 (Mcm-2), activated caspase-3 (a-casp3) and Bcl-2 to determine if they showed differential expression across progressive degrees of intraepithelial neoplasia and cancer in the prostate. To identify field effects, we also evaluated whether high-risk expression patterns in normal tissue were more common in prostates containing cancer compared to those without cancer (supernormal), and in histologically normal glands adjacent to a cancer focus as opposed to equivalent glands that were more distant. METHODS: The aforementioned markers were studied in 13 radical prostatectomy (RP) and 6 cystoprostatectomy (CP) specimens. Tissue compartments representing normal, low grade prostatic intraepithelial neoplasia (LGPIN), high grade prostatic intraepithelial neoplasia (HGPIN), as well as different grades of cancer were mapped on H&E slides and adjacent sections were analyzed using immunohistochemistry. Normal glands within 1 mm distance of a tumor focus and glands beyond 5 mm were considered "near" and "far", respectively. Randomly selected nuclei and 40 × fields were scored by a single observer; basal and luminal epithelial layers were scored separately. RESULTS: Both Ki-67 and Mcm-2 showed an upward trend from normal tissue through HGPIN and cancer with a shift in proliferation from basal to luminal compartment. Activated caspase-3 showed a significant decrease in HGPIN and cancer compartments. Supernormal glands had significantly lower proliferation indices and higher a-casp3 expression compared to normal glands. "Near" normal glands had higher Mcm-2 indices compared to "far" glands; however, they also had higher a-casp3 expression. Bcl-2, which varied minimally in normal tissue, did not show any trend across compartments or evidence for field effects. CONCLUSION: These results demonstrate that proliferation and apoptosis are altered not only in preneoplastic lesions but also in apparently normal looking epithelium associated with cancer. Luminal cell expression of Mcm-2 appears to be particularly promising as a marker of high-risk normal epithelium. The role of apoptotic markers such as activated caspase-3 is more complex, and might depend on the proliferation status of the tissue in question

Effects of whey protein alone or as part of a multi-ingredient formulation on strength, fat-free mass, or lean body mass in resistance-trained individuals: A meta-analysis

BACKGROUND: Even though the positive effects of whey protein-containing supplements for optimizing the anabolic responses and adaptations process in resistance-trained individuals have been supported by several investigations, their use continues to be controversial. Additionally, the administration of different multi-ingredient formulations where whey proteins are combined with carbohydrates, other protein sources, creatine, and amino acids or derivatives, has been extensively proposed as an effective strategy to maximize strength and muscle mass gains in athletes. OBJECTIVE: We aimed to systematically summarize and quantify whether whey protein-containing supplements, administered alone or as a part of a multi-ingredient, could improve the effects of resistance training on fat-free mass or lean body mass, and strength in resistance-trained individuals when compared with other iso-energetic supplements containing carbohydrates or other sources of proteins. METHODS: A structured literature search was conducted on PubMed, Science Direct, Web of Science, Cochrane Libraries, US National Institutes of Health clinicaltrials.gov, SPORTDiscus, and Google Scholar databases. Main inclusion criteria comprised randomized controlled trial study design, adults (aged 18 years and over), resistance-trained individuals, interventions (a resistance training program for a period of 6 weeks or longer, combined with whey protein supplementation administered alone or as a part of a multi-ingredient), and a calorie equivalent contrast supplement from carbohydrates or other non-whey protein sources. Continuous data on fat-free mass and lean body mass, and maximal strength were pooled using a random-effects model. RESULTS: Data from nine randomized controlled trials were included, involving 11 treatments and 192 participants. Overall, with respect to the ingestion of contrast supplements, whey protein supplementation, administered alone or as part of a multi-ingredient, in combination with resistance training, was associated with small extra gains in fat-free mass or lean body mass, resulting in an effect size of g = 0.301, 95% confidence interval (CI) 0.032-0.571. Subgroup analyses showed less clear positive trends resulting in small to moderate effect size g = 0.217 (95% CI -0.113 to 0.547) and g = 0.468 (95% CI 0.003-0.934) in favor of whey and multi-ingredient, respectively. Additionally, a positive overall extra effect was also observed to maximize lower (g = 0.316, 95% CI 0.045-0.588) and upper body maximal strength (g = 0.458, 95% CI 0.161-0.755). Subgroup analyses showed smaller superiority to maximize strength gains with respect to the contrast groups for lower body (whey protein: g = 0.343, 95% CI -0.016 to 0.702, multi-ingredient: g = 0.281, 95% CI -0.135 to 0.697) while in the upper body, multi-ingredient (g = 0.612, 95% CI 0.157-1.068) seemed to produce more clear effects than whey protein alone (g = 0.343, 95% CI -0.048 to 0.735). LIMITATIONS: Studies involving interventions of more than 6 weeks on resistance-training individuals are scarce and account for a small number of participants. Furthermore, no studies with an intervention longer than 12 weeks have been found. The variation regarding the supplementation protocol, namely the different doses criteria or timing of ingestion also add some concerns to the studies comparison. CONCLUSIONS: Whey protein alone or as a part of a multi-ingredient appears to maximize lean body mass or fat-free mass gain, as well as upper and lower body strength improvement with respect to the ingestion of an iso-energetic equivalent carbohydrate or non-whey protein supplement in resistance-training individuals. This enhancement effect seems to be more evident when whey proteins are consumed within a multi-ingredient containing creatine

Burnout among chiropractic practitioners: real or imagined an exploratory study protocol

Burnout is a psychological syndrome of emotional exhaustion, depersonalization and reduced personal accomplishment that has been found to exist in a significant number of healthcare and helping professionals. It imposes a significant societal burden by shortened practitioner lifespan, decreased efficiency, negative health outcomes and poorer levels of patient care. Theoretical models suggest that it appears to be the result of a complex interaction between job resources and job demands. It may be reasonable to conclude that Chiropractic professionals experience similar vocational demands and thus experience significant levels of occupational stress and subsequent burnout. However the data on burnout within the chiropractic profession is limited. It is possible that this results in significant negative outcomes on chiropractors and their patients. Therefore, the objective of this paper is to demonstrate the need to explore burnout in chiropractic practice and offer a research protocol for a potential study

Characterization of an Nmr Homolog That Modulates GATA Factor-Mediated Nitrogen Metabolite Repression in Cryptococcus neoformans

Nitrogen source utilization plays a critical role in fungal development, secondary metabolite production and pathogenesis. In both the Ascomycota and Basidiomycota, GATA transcription factors globally activate the expression of catabolic enzyme-encoding genes required to degrade complex nitrogenous compounds. However, in the presence of preferred nitrogen sources such as ammonium, GATA factor activity is inhibited in some species through interaction with co-repressor Nmr proteins. This regulatory phenomenon, nitrogen metabolite repression, enables preferential utilization of readily assimilated nitrogen sources. In the basidiomycete pathogen Cryptococcus neoformans, the GATA factor Gat1/Are1 has been co-opted into regulating multiple key virulence traits in addition to nitrogen catabolism. Here, we further characterize Gat1/Are1 function and investigate the regulatory role of the predicted Nmr homolog Tar1. While GAT1/ARE1 expression is induced during nitrogen limitation, TAR1 transcription is unaffected by nitrogen availability. Deletion of TAR1 leads to inappropriate derepression of non-preferred nitrogen catabolic pathways in the simultaneous presence of favoured sources. In addition to exhibiting its evolutionary conserved role of inhibiting GATA factor activity under repressing conditions, Tar1 also positively regulates GAT1/ARE1 transcription under non-repressing conditions. The molecular mechanism by which Tar1 modulates nitrogen metabolite repression, however, remains open to speculation. Interaction between Tar1 and Gat1/Are1 was undetectable in a yeast two-hybrid assay, consistent with Tar1 and Gat1/Are1 each lacking the conserved C-terminus regions present in ascomycete Nmr proteins and GATA factors that are known to interact with each other. Importantly, both Tar1 and Gat1/Are1 are suppressors of C. neoformans virulence, reiterating and highlighting the paradigm of nitrogen regulation of pathogenesis