Human Papilloma Virus Positive Oropharyngeal Squamous Cell Carcinoma and the Immune System: Pathogenesis, Immunotherapy and Future Perspectives.

Oropharyngeal squamous cell carcinoma (OPSCC), a subset of head and neck squamous cell carcinoma (HNSCC), involves the palatine tonsils, soft palate, base of tongue, and uvula, with the ability to spread to adjacent subsites. Personalized treatment strategies for Human Papillomavirus-associated squamous cell carcinoma of the oropharynx (HPV+OPSCC) are yet to be established. In this article, we summarise our current understanding of the pathogenesis of HPV+OPSCC, the intrinsic role of the immune system, current ICI clinical trials, and the potential role of small molecule immunotherapy in HPV+OPSCC.

How exercise affects lipid profiles in women: what to recommend for patients.

After menopause, women have less favorable lipid profiles than before menopause. While regular exercise improves lipid metabolism in men, the specifics for doing so in pre- and postmenopausal women are not fully understood. Literature review suggests that higher-volume aerobic exercise programs increase high-density lipoprotein cholesterol (HDL-C) levels in both pre- and postmenopausal women. Although longitudinal studies of resistance training did not reveal increases in HDL-C levels in women, other favorable benefits observed included decreases in low-density lipoprotein-cholesterol, total cholesterol, and body fat. Cross-sectional studies, however, seem to favor high-volume exercise for increasing HDL-C levels.

Effect of 14 weeks of resistance training on lipid profile and body fat percentage in premenopausal women.

OBJECTIVES: To study the effects of a supervised, intensive (85% of one repetition maximum (1-RM)) 14 week resistance training programme on lipid profile and body fat percentage in healthy, sedentary, premenopausal women. SUBJECTS: Twenty four women (mean (SD) age 27 (7) years) took part in the study. Subjects were randomly assigned to either a non-exercising control group or a resistance exercise training group. The resistance exercise training group took part in supervised 45-50 minute resistance training sessions (85% of 1-RM), three days a week on non-consecutive days for 14 weeks. The control group did not take part in any structured physical activity. RESULTS: Two way analysis of variance with repeated measures showed significant (p < 0.05) increases in strength (1-RM) in the exercising group. There were significant (p < 0.05) decreases in total cholesterol (mean (SE) 4.68 (0.31) v 4.26 (0.23) mmol/1 (180 (12) v 164 (9) mg/dl)), low density lipoprotein (LDL) cholesterol (2.99 (0.29) v 2.57 (0.21) mmol/l (115 (11) v 99 (8) mg/dl), the total to high density lipoprotein (HDL) cholesterol ratio (4.2 (0.42) v 3.6 (0.42)), and body fat percentage (27.9 (2.09) v 26.5 (2.15)), as well as a strong trend towards a significant decrease in the LDL to HDL cholesterol ratio (p = 0.057) in the resistance exercise training group compared with their baseline values. No differences were seen in triglycerides and HDL cholesterol. No changes were found in any of the measured variables in the control group. CONCLUSIONS: These findings suggest that resistance training has a favourable effect on lipid profile and body fat percentage in healthy, sedentary, premenopausal women.

The effect of oral creatine monohydrate supplementation on running velocity.

Creatine supplementation has been shown to augment muscle PCr content and increase the rate of ATP resynthesis. Thus, we hypothesized that creatine supplementation might enhance sprinting performance. Eighteen subjects completed both of two testing sessions (control and postsupplement) 1 week apart, wherein they sprinted three 60-m distance trials that were recorded with videotape. Following the control session, for 7 days, subjects in the treatment group ingested a creatine-glucose mixture, while the placebo group consumed a glucose powder, followed by the postsupplementation session. Velocities of the subjects through three testing zones within the 60-m sprint were calculated from the videotape. Resultant velocities were analyzed using a MANOVA with a 2 x 2 x 3 x 3 (Group x Session x Trial x Zone) design. Results indicated that there were no statistically significant main or interaction effects on velocity between groups for session, trial, or zone. These data do not support the hypothesis that supplementary creatine ingestion will enhance velocity during the early or latter segments of a 60-m sprint.

Effect of Eleutherococcus senticosus on submaximal and maximal exercise performance.

We investigated the effect of Eleutherococcus senticosus Maxim L (ESML) on performance during submaximal and maximal aerobic exercise. Twenty highly trained distance runners randomly assigned in matched pairs to either an experimental (ESML) or placebo (PL) group, participated in an 8-wk double-blind study during which they completed five trails of a 10-min treadmill run at their 10 km (10K) race pace and a maximal treadmill test (T(max)). Following a baseline trail, ESML and PL consumed, respectively, 3.4 ml of ESML extract or placebo daily for 6 wk. Subjects were tested every 2 wk during supplementation and 2 wk following withdrawal. Heart rate (HR), oxygen consumption (VO2), expired minute volume (VE), ventilatory equivalent for oxygen (VE/VO2), respiratory exchange ratio (RER), and rating of perceived exertion (RPE) were measured during the 10K and T(max) tests. Resting, post-10K and post-T(max) blood samples were analyzed for serum lactate. No significant differences were observed between ESML and PL for: HR, VO2, VE, VE/VO2, RER, or RPE; T(max) time to exhaustion; or serum lactate. The data do not support an ergogenic effect of ESML supplementation on selected metabolic, performance, or psychologic parameters associated with submaximal and maximal aerobic exercise tasks.

Isodicentric Y chromosome: cytogenetic, molecular and clinical studies and review of the literature.

Dicentrics are among the most common structural abnormalities of the human Y chromosome. Predicting the phenotypic consequences of different duplications and deletions of dicentric Y chromosomes is usually complicated by varying degrees of mosaicism (45,X cell lines), which may, in some cases, remain undetected. Molecular studies in patients with dicentric Y chromosomes have been few, and only two studies have attempted to determine the presence of SRY (the putative testis-determining factor gene). We report an 18-year-old female with short stature, amenorrhea, hirsutism, hypoplastic labia minora, and clitoromegaly who has a 45,X/46,X,idic(Y)(p11.32)/47,X,idic(Y)(p11.32),idic(Y) (p11.32) karyotype. Southern analysis using Y-specific probes (Y97, 2D6, 1F5, pY3.4) and polymerase chain reaction (PCR) analysis using primers for ZFY and SRY were positive for all loci tested, indicating that almost all of the Y chromosome was present. Our findings and an extensive review of the literature emphasize the importance of molecular analyses of abnormal Y chromosomes before any general conclusions can be reached concerning the relative effects of the Y-chromosome abnormality and mosaicism on sexual differentiation.

Time-frequency analyses of thyroarytenoid myoelectric activity in normal and spasmodic dysphonia subjects.

Digital recordings of thyroarytenoid (TA) myoelectric activity (via percutaneous hooked-wire electrodes) were obtained for 10 normal control subjects and 10 subjects with spasmodic dysphonia during performance of five tasks of varying complexity: quiet breathing, Valsalva maneuver, whispered /i/, voiced /i/, and "beep beep went the heap." Time-frequency power spectral density functions, PSD(f,t), were determined for a selected segment of the signals, and measures of median frequency, mean frequency, bandwidth, and center frequency of PSD(f,t) were derived for each sample point. Statistical median, mean, standard deviation, minimum, maximum, and mode of the power spectral density measures were computed to compose feature vectors for each TA myoelectric recording. Statistical pattern recognition procedures using maximum likelihood classification tests were applied to the feature space to discriminate disordered from normal speakers for each task. Findings indicate a high level of discriminability between subject groups for phonated speaking tasks in contrast to low levels of discriminability for whispered and nonspeech tasks. Graphical presentations of three-dimensional PSD(f,t) plots are given that illustrate changes in spectral characteristics of TA EMG at the onset of laryngospasm.

Teaching immediate cardiac care to general practitioners: a faculty-based approach.

This paper describes the development, piloting and delivery of an immediate care cardiac course (ICCC) to Irish general practitioners. The course utilizes the continuing medical education network of the Irish College of General Practitioners. This has made the course locally accessible even for remote practitioners and has facilitated rapid dissemination. In its first year, 167 GPs (8% of the total number of Irish GPs) have completed the course. Participant feedback has been positive, especially regarding the small group- and skills-based components. The introduction of more formal assessment procedures is now being undertaken. We believe this model to be a possible template for the introduction of other skills courses both in Ireland and abroad.

Postsurgical timing of restorative therapy: a review.

Knowledge of wound healing is necessary for the clinician when determining the time of prosthodontic treatment after periodontal surgery. Wound healing and longitudinal clinical studies indicate that the clinician should wait approximately 8 weeks before proceeding with the final restoration. Restorative procedures could be considered as early as 6 weeks if (1) the patient shows good systemic health; (2) injury is not inflicted on the gingiva by the restorative technique; (3) restorative margins are supragingival; and (4) esthetics are not critical. With a thick periodontium, more common in posterior areas, the gingiva often will move coronally as the tissue matures. Thin periodontal tissues may recede postsurgically, and in areas of esthetic concern, postponement of final restoration for up to 5 to 6 months may be desirable to assure gingival margin stability. Modifiers that may affect time and quality of healing, such as the patient's smoking frequency and age, should be considered when scheduling restorative treatment after periodontal surgery.

Effects of acute caffeine withdrawal on habituated male runners.

This study investigated the effects of caffeine withdrawal on six trained caffeine-habituated male runners: age 29.8 +/- 5.8 (SD) yr, height 180.4 +/- 5.4 cm, weight 77.3 +/- 6.7 kg, maximal O2 uptake 63.0 +/- 5.4 ml.kg-1.min-1, and daily caffeine intake 674 +/- 128 mg. The subjects received a loading dose (5 mg/kg body wt) of caffeine 48 h before each testing session. They were then given (using a repeated-measures double-blind design) additional doses of caffeine (5 mg/kg body wt) or a placebo 36, 24, 12, and 2 h before testing. They ran at a velocity corresponding to their lactate threshold for 60 min in a caffeine withdrawal or caffeinated condition. Caffeine withdrawal resulted in no significant differences in absolute O2 uptake, O2 uptake relative to maximal O2 uptake, respiratory exchange ratios, or free fatty acid concentrations. Glycerol concentrations were significantly attenuated in the withdrawal condition. No significant differences were revealed in calculated substrate utilization. It was concluded that caffeine withdrawal significantly affects lipolysis but not substrate utilization during prolonged running.

Assessment of a human recombinant manganese superoxide dismutase in models of inflammation.

We evaluated a novel human recombinant preparation of manganese superoxide dismutase (MnSOD) for anti-inflammatory and anti-oxidant activity compared with a copper zinc (CuZn) SOD preparation. The results showed that administration of MnSOD (50, 100 and 200 micrograms kg-1) in the Freund's Complete Adjuvant (FCA) mediated paw oedema model suppressed the inflammation at 4 hours by 43, 25 and 43% (P < 0.001, P < 0.01 and P < 0.001 at respective doses). However, 24 hours post-challenge, MnSOD (50 and 100 micrograms kg-1), suppressed the inflammation by 19% (P < 0.001). In contrast, Mn SOD at higher doses (400-800 micrograms kg-1; 2 mgkg-1) exacerbated the inflammatory response at 4 hours. This pro-inflammatory response declined progressively by 24 hours. Furthermore, CuZn SOD produced no significant effects on the inflammatory response. In the carrageenan-induced synovitis model, Mn SOD (25 and 50 micrograms; intra-articular administration) exacerbated the inflammation at 48 hours. In contrast, Mn SOD at 5 micrograms produced a significant suppression (44%, P < 0.05) in knee joint swelling at 24 hours. The CuZn SOD preparation produced marked pro-inflammatory effects in the joints whilst it lacked activity in the FCA-mediated paw oedema model. These findings support a therapeutic potential of MnSOD in inflammatory disorders, however the compound has a complex pharmaco-dynamic profile.

Chondromyxoid fibroma.

Chondromyxoid fibroma (CMF) is the least common cartilage-producing tumor. In Dahlin and Unni's series of 8,542 bone tumors, 39 of which were CMF, none were found in the femoral shaft. In this case, a CMF in the femoral shaft presented initially as a pathologic fracture. Attempts at curettage and autogenous bone graft failed, and en bloc resection and segmented allograft reconstruction were eventually required.

Reproductive hormones and bone mineral density in women runners.

We examined the relationships among reproductive hormone concentrations and bone mineral density (BMD) in 43 women runners classified as eumenorrheic (n = 24), oligomenorrheic (n = 8), or amenorrheic (n = 11). Results were compared with a eumenorrheic nonrunner control group (n = 11). Serum 17 beta-estradiol, progesterone, and dehydroepiandrosterone sulfate concentrations were determined in daily blood samples for 21 days, and integrated concentrations (areas under the curve) were calculated. BMD was assessed at the lumbar spine and proximal femur by dual-photon absorptiometry. As expected, 17 beta-estradiol, progesterone, and lumbar spine BMD were higher in the control and eumenorrheic runner groups than in the oligomenorrheic and amenorrheic runner groups (P less than 0.05). Progesterone concentration was significantly correlated with lumbar spine BMD in the eumenorrheic runners (r = 0.61). None of the steroid hormones was significantly related to BMD in the oligomenorrheic/amenorrheic group. The present data suggest that circulating levels of gonadal steroid hormones affect axial BMD in eumenorrheic runners.

The selective protection afforded by ebselen against lipid peroxidation in an ROS-dependent model of inflammation.

The effects of an experimental model of hydrogen-peroxide-induced foot pad oedema on indices of oxidative damage to biomolecules have been investigated. We have demonstrated increased levels of fluorescent protein and lipid peroxides occurring in plasma at 24 and 48 h post-injection. In addition, a decrease in the degree of galactosylation of IgG was observed which kinetically related the degree of inflammation and to the increase in protein autofluorescence (a specific index of oxidative damage). The effects of ebselen, a novel organoselenium compound which protects against oxidative tissue injury in a glutathione-peroxidase-like manner, have also been examined in this model. Pretreatment of animals with a dose of 50 mg/kg ebselen afforded significant and selective protection against lipid peroxidation only. This effect may contribute to the anti-inflammatory effect of this agent in hydroperoxide-linked tissue damage.

Durability of the reproductive axis in eumenorrheic women during 1 yr of endurance training.

Menstrual cycle (MC) alterations occur in some endurance-training women. We hypothesized that a prospective running program would evoke alterations in MC phase lengths and in the physiological frequency of pulses of luteinizing hormone (LH) and/or diminish 24-h integrated serum LH concentrations in some women. In addition, we postulated that women who train more intensively (above the lactate threshold) would show alterations in gonadotropin release earlier in the training program or to a greater degree. To test these hypotheses, we examined the effects of different exercise intensities on physiological and endocrine responses. Twenty-three healthy eumenorrheic gynecologically mature (postmenarchal age 17.8 +/- 0.9 yr) untrained women undertook a 1-yr training program at one of two exercise intensities, one at a velocity corresponding to the lactate threshold (LT) and the other halfway between that of LT and peak running velocity, or served as controls. Training distance was the same in each exercise group. Physiological measurements were repeated every four MC to track changes in fitness and readjust training velocities. The lengths of the MC and the follicular and luteal phases were determined from hormonal concentrations. Body composition, nutritional intake, and pulsatile release of LH were determined. The women ran approximately 790 miles. Each group improved physiologically, with the greater than LT group improving to a greater degree. A less than 2-day decrease in the luteal phase length was observed only in the greater than LT group. No significant changes for any parameter of pulsatile LH release were noted between exercise groups. No significant changes in nutritional intake and only small changes in body composition were noted in either exercise group despite the added energy expenditure of exercise. We conclude that a progressive exercise program of moderate distance and intensity does not adversely affect the robust reproductive system of gynecologically mature eumenorrheic women.

Endometrial morphology in asymptomatic postmenopausal women.

Few data are available regarding endometrial histologic features in asymptomatic perimenopausal and postmenopausal women. This study encompasses endometrial biopsy specimens obtained from 801 such women before enrollment in a multicenter study of estrogen-progestin replacement. One endometrial cancer was found (0.13%); four additional biopsy specimens showed atypia (total 0.63%). The endometrium was atrophic in 373 (46.9%), proliferative in 133 (16.7%), secretory in 54 (6.8%), and hyperplastic in 41 (5.2%). Insufficient tissue for diagnosis was obtained in 195 (24.5%). We conclude that the yield for neoplasia is so low that screening endometrial biopsy is not justified in asymptomatic perimenopausal and postmenopausal women.