Natural trait variation across Saccharomycotina species.

Among molecular biologists, the group of fungi called Saccharomycotina is famous for its yeasts. These yeasts in turn are famous for what they have in common-genetic, biochemical, and cell-biological characteristics that serve as models for plants and animals. But behind the apparent homogeneity of Saccharomycotina species lie a wealth of differences. In this review, we discuss traits that vary across the Saccharomycotina subphylum. We describe cases of bright pigmentation; a zoo of cell shapes; metabolic specialties; and species with unique rules of gene regulation. We discuss the genetics of this diversity and why it matters, including insights into basic evolutionary principles with relevance across Eukarya.

Do proximal hip geometry, trabecular microarchitecture, and prevalent vertebral fractures differ in postmenopausal women with type 2 diabetes mellitus? A cross-sectional study from a teaching hospital in southern India.

This study from southern India showed that the trabecular microarchitecture and proximal hip geometry were significantly impaired in postmenopausal women with diabetes as compared to age and BMI matched non-diabetic controls. This is despite there being no significant difference in bone mineral density at the femoral neck and hip not between both groups. One-third of the study subjects with type 2 diabetes had prevalent vertebral fractures. Bone mineral density assessment as a standalone tool may not adequately reflect bone health in subjects with diabetes. INTRODUCTION: There is limited information with regard to bone health in Indian postmenopausal women with type 2 diabetes. We studied the bone mineral density (BMD), trabecular bone score (TBS), prevalent vertebral fractures (VF), proximal hip geometry, and bone mineral biochemistry in ambulatory postmenopausal women with and without type 2 diabetes mellitus (T2DM). METHODS: This was a cross-sectional study conducted at a tertiary care center. BMD, TBS, prevalent vertebral fractures, and hip structural analysis (HSA) were assessed using a dual-energy X-ray absorptiometry (DXA) scanner. Bone mineral biochemical profiles were also studied. RESULTS: A total of 202 ambulatory postmenopausal women known to have type 2 diabetes mellitus with mean (SD) age of 65.6 (5.2) years and 200 age and BMI matched non-diabetic controls with mean (SD) age of 64.9 (4.7) years were recruited from the local community. Although the prevalence of lumbar spine osteoporosis was significantly lower among cases (30.7%) as compared to controls (42.9%), the prevalence of degraded bone microarchitecture (TBS < 1.200) was significantly higher among cases (51%) than in controls (23.5%); P < 0.001. Prevalent vertebral fractures were not significantly different in cases and controls. The various geometric indices of the proximal hip were significantly impaired in subjects with diabetes as compared to controls. CONCLUSION: This study may highlight the utility of the trabecular bone score and hip structural analysis in subjects with diabetes, where the bone mineral density tends to be paradoxically high, and may not adequately predict fracture risk.

Phase II trial of post-operative radiotherapy with concurrent cisplatin plus panitumumab in patients with high-risk, resected head and neck cancer.

BACKGROUND: Treatment intensification for resected, high-risk, head and neck squamous cell carcinoma (HNSCC) is an area of active investigation with novel adjuvant regimens under study. In this trial, the epidermal growth-factor receptor (EGFR) pathway was targeted using the IgG2 monoclonal antibody panitumumab in combination with cisplatin chemoradiotherapy (CRT) in high-risk, resected HNSCC. PATIENTS AND METHODS: Eligible patients included resected pathologic stage III or IVA squamous cell carcinoma of the oral cavity, larynx, hypopharynx, or human-papillomavirus (HPV)-negative oropharynx, without gross residual tumor, featuring high-risk factors (margins <1 mm, extracapsular extension, perineural or angiolymphatic invasion, or ≥2 positive lymph nodes). Postoperative treatment consisted of standard RT (60-66 Gy over 6-7 weeks) concurrent with weekly cisplatin 30 mg/m2 and weekly panitumumab 2.5 mg/kg. The primary endpoint was progression-free survival (PFS). RESULTS: Forty-six patients were accrued; 44 were evaluable and were analyzed. The median follow-up for patients without recurrence was 49 months (range 12-90 months). The probability of 2-year PFS was 70% (95% CI = 58%-85%), and the probability of 2-year OS was 72% (95% CI = 60%-87%). Fourteen patients developed recurrent disease, and 13 (30%) of them died. An additional five patients died from causes other than HNSCC. Severe (grade 3 or higher) toxicities occurred in 14 patients (32%). CONCLUSIONS: Intensification of adjuvant treatment adding panitumumab to cisplatin CRT is tolerable and demonstrates improved clinical outcome for high-risk, resected, HPV-negative HNSCC patients. Further targeted monoclonal antibody combinations are warranted. REGISTERED CLINICAL TRIAL NUMBER: NCT00798655.

Phase II randomized trial of radiation therapy, cetuximab, and pemetrexed with or without bevacizumab in patients with locally advanced head and neck cancer.

BACKGROUND: We previously reported the safety of concurrent cetuximab, an antibody against epidermal growth factor receptor (EGFR), pemetrexed, and radiation therapy (RT) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). In this non-comparative phase II randomized trial, we evaluated this non-platinum combination with or without bevacizumab, an inhibitor of vascular endothelial growth factor (VEGF). PATIENTS AND METHODS: Patients with previously untreated stage III-IVB SCCHN were randomized to receive: conventionally fractionated radiation (70 Gy), concurrent cetuximab, and concurrent pemetrexed (arm A); or the identical regimen plus concurrent bevacizumab followed by bevacizumab maintenance for 24 weeks (arm B). The primary end point was 2-year progression-free survival (PFS), with each arm compared with historical control. Exploratory analyses included the relationship of established prognostic factors to PFS and quality of life (QoL). RESULTS: Seventy-eight patients were randomized: 66 oropharynx (42 HPV-positive, 15 HPV-negative, 9 unknown) and 12 larynx; 38 (49%) had heavy tobacco exposure. Two-year PFS was 79% [90% confidence interval (CI) 0.69-0.92; P < 0.0001] for arm A and 75% (90% CI 0.64-0.88; P < 0.0001) for arm B, both higher than historical control. No differences in PFS were observed for stage, tobacco history, HPV status, or type of center (community versus academic). A significantly increased rate of hemorrhage occurred in arm B. SCCHN-specific QoL declined acutely, with marked improvement but residual symptom burden 1 year post-treatment. CONCLUSIONS: RT with a concurrent non-platinum regimen of cetuximab and pemetrexed is feasible in academic and community settings, demonstrating expected toxicities and promising efficacy. Adding bevacizumab increased toxicity without apparent improvement in efficacy, countering the hypothesis that dual EGFR-VEGF targeting would overcome radiation resistance, and enhance clinical benefit. Further development of cetuximab, pemetrexed, and RT will require additional prospective study in defined, high-risk populations where treatment intensification is justified.

Negative predictive value of surveillance PET/CT in head and neck squamous cell cancer.

BACKGROUND AND PURPOSE: Optimizing the utilization of surveillance PET/CT in treated HNSCC is an area of ongoing research. Our aim was to determine the negative predictive value of PET/CT in patients with treated head and neck squamous cell cancer and to determine whether negative PET/CT reduces the need for further imaging surveillance. MATERIALS AND METHODS: We evaluated patients with treated HNSCC who underwent posttreatment surveillance PET/CT. During routine clinical readouts, scans were categorized as having negative, probably negative, probably malignant, or malignant findings. We followed patients clinically and radiographically for at least 12 months from their last PET/CT (mean, 26 months; median, 28 months; range, 12-89 months) to determine recurrence rates. All suspected recurrences underwent biopsy for confirmation. RESULTS: Five hundred twelve patients (1553 scans) were included in the study. Two hundred fourteen patients had at least 1 PET/CT with negative findings. Of the 214 patients with a scan with negative findings, 19 (9%) eventually experienced recurrence, resulting in a NPV of 91%. In addition, a subgroup of 114 patients with 2 consecutive PET/CT examinations with negative findings within a 6-month period was identified. Only 2 recurrences were found in this group, giving a NPV of 98%. CONCLUSIONS: In patients treated for HNSCC, a single PET/CT with negative findings carries a NPV of 91%, which is not adequate to defer further radiologic surveillance. Two consecutive PET/CT examinations with negative findings within a 6-month period, however, resulted in a NPV of 98%, which could obviate further radiologic imaging in the absence of clinical signs of recurrence.

Fast-neutron spectrometry using a ³He ionization chamber and digital pulse shape analysis.

Digital pulse shape analysis (dPSA) has been used with a Cuttler-Shalev type (3)He ionization chamber to measure the fast-neutron spectra of a deuterium-deuterium electronic neutron generator, a bare (252)Cf spontaneous fission neutron source, and of the transmitted fast neutron spectra of a (252)Cf source attenuated by water, graphite, liquid nitrogen, and magnesium. Rise-time dPSA has been employed using the common approach for analyzing n +(3)He→(1)H+(3)H ionization events and improved to account for wall-effect and pile-up events, increasing the fidelity of these measurements. Simulations have been performed of the different experimental arrangements and compared with the measurements, demonstrating general agreement between the dPSA-processed fast-neutron spectra and predictions. The fast-neutron resonance features of the attenuation cross sections of the attenuating materials are clearly visible within the resolution limits of the electronics used for the measurements, and the potential applications of high-resolution fast-neutron spectrometry for nuclear nonproliferation and safeguards measurements are discussed.

Phase I trial of pemetrexed in combination with cetuximab and concurrent radiotherapy in patients with head and neck cancer.

BACKGROUND: We studied the combination of pemetrexed, a multi-targeted antifolate, and cetuximab, an mAb against the epidermal growth factor receptor, with radiotherapy in poor prognosis head and neck cancer. PATIENTS AND METHODS: Patients received pemetrexed on days 1, 22, and 43 on a dose-escalation scheme with starting level (0) 350 mg/m(2) (level -1, 200 mg/m(2); level +1, 500 mg/m(2)) with concurrent radiotherapy (2 Gy/day) and cetuximab in two separate cohorts, not previously irradiated (A) and previously irradiated (B), who received 70 and 60-66 Gy, respectively. Genetic polymorphisms of thymidylate synthase and methylenetetrahydrofolate reductase were evaluated. RESULTS: Thirty-two patients were enrolled. The maximum tolerated dose of pemetrexed was 500 mg/m(2) in cohort A and 350 mg/m(2) in cohort B. Prophylactic antibiotics were required. In cohort A, two dose-limiting toxicities (DLTs) occurred (febrile neutropenia), one each at levels 0 and +1. In cohort B, two DLTs occurred at level +1 (febrile neutropenia; death from perforated duodenal ulcer and sepsis). Grade 3 mucositis was common. No association of gene polymorphisms with toxicity or efficacy was evident. CONCLUSION: The addition of pemetrexed 500 mg/m(2) to cetuximab and radiotherapy is recommended for further study in not previously irradiated patients.

Response assessment by combined PET-CT scan versus CT scan alone using RECIST in patients with locally advanced head and neck cancer treated with chemoradiotherapy.

PURPOSE: RECIST have limitations when applied to potentially curable locally advanced squamous cell carcinoma of the head and neck (SCCHN). [¹8F]fluorodeoxyglucose-positron emission tomography (PET) scan may be useful in assessing treatment response and predicting patient outcome. PATIENTS AND METHODS: We studied patients with previously untreated stages III-IVb SCCHN treated with primary concurrent chemoradiotherapy on five prospective clinical trials. Response was assessed by clinical exam, computed tomography (CT), and PET portions of combined PET-CT scan ∼8 weeks after completion of chemoradiotherapy. RESULTS: Fifty-three patients were analyzed. Complete response (CR) was demonstrated in 42 patients (79%) by clinical exam, 15 (28%) by CT, and 27 (51%) by PET. CR as assessed by PET, but not as assessed by clinical exam or CT using RECIST, correlated significantly with progression-free status (PFS) (P < 0.0001). The 2-year PFS for patients with CR and without CR by PET was 93% and 48%, respectively (P = 0.0002). CONCLUSIONS: A negative PET scan on combined PET-CT after chemoradiotherapy is a powerful predictor of outcome in patients receiving curative chemoradiotherapy for SCCHN. PET-CT is indicated for response evaluation in this setting to improve the accuracy of post-treatment assessment by CT.

Osteoblastoma of the hyoid bone.

Osteoblastoma is a rare bone tumor that usually affects the vertebrae. We present the first known case of osteoblastoma arising in the hyoid bone, in a patient who presented with a neck mass and dysphagia. The radiographic appearance of the tumor is similar to that of low-grade chondrosarcoma, with well-defined expansion of the bone and central chondroid matrix.

Patient safety on the otolaryngology service: the role of an established rapid response system.

OBJECTIVE: To study the medical emergencies occurring on a tertiary otolaryngology service identified using a rapid response system (RRS). DESIGN: Retrospective chart review of RRS activations during 21 months. SETTING: Specialised otolaryngology care unit within the University of Pittsburgh Medical Center Presbyterian/Montefiore Hospital, a tertiary, academic, teaching hospital in the USA. INTERVENTION(S): None. RESULTS: 1171 unit admissions. Unit mortality was 5.1/1000 admissions. 53 patients were involved in 67 RRS activations (4/53 deaths). 32 of 67 events were due to respiratory derangements, most commonly pneumonia. 18 of 67 events were due to cardiovascular abnormalities, most commonly hypertension and myocardial infarction. 11 of 67 events were secondary to mental status changes, several of which were related to adverse drug events. 6 of 67 events were secondary to acute bleeding. 23 of 67 events occurred within 24 h of patient transfer/admission, 14 of those after operations. RRS activation was a marker for in-hospital death (RR 42.2, 95% CI 7.9 to 225.2) compared with that in patients not activating the RRS. CONCLUSIONS: Although otolaryngology care units attempt to prevent adverse events, emergencies still occur. RRSs identify deteriorating otolaryngology patients who are at increased risk for mortality. RRSs are an efficient mechanism of intervention during a medical emergency. RRSs provide a convenient method of identifying medical/system errors and educational opportunities.

Theory of planned behavior and multivitamin supplement use in Caucasian college females.

The objective of this study was to identify predictors of the use of multivitamin supplements (MVS) among Caucasian college females utilizing the Theory of Planned Behavior (TPB). Variables of the TPB and the self-reported use of multivitamin supplements were measured by two separate surveys within 1 week with a convenience sample of 96 Caucasian college student females. Two attitudinal beliefs and one control belief significantly predicted behavioral intention to use multivitamin. A belief that taking multivitamin supplements helps to feel and look good was the most important predictor of the use of multivitamin supplements. EDITORS' STRATEGIC IMPLICATIONS: Findings from this study, although in need of replication, suggest that prevention campaigns would be more successful if messages used to reach these females were consistent with perceived beliefs regarding benefits of using MVS. More broadly, TPB appears to offer a useful framework for understanding or predicting behavior based on psychological constructs theorized to influence behavior.

Role of limited parotidectomy in management of pleomorphic adenoma.

There is continued controversy over the extent of parotidectomy required for removal of a benign pleomorphic adenoma from the parotid gland. Currently, consensus exists that the integrity of the facial nerve must be preserved when the tumour is totally removed. As a result of experience gained in the first half of the twentieth century, it was recommended that superficial parotidectomy with facial nerve dissection should be the minimal biopsy for pleomorphic adenoma. Since that time, however, research has indicated that partial parotidectomy or extracapsular dissection of benign pleomorphic adenoma can be accomplished with preservation of the facial nerve without an increase in tumour recurrence. Partial parotidectomy or extracapsular dissection results in impaired cosmetic results and a lower incidence of Frey's syndrome, and thus may be the preferred approach when undertaken by experienced surgeons.

Influence of range of motion in resistance training in women: early phase adaptations.

The purpose of this investigation was to compare partial range-of-motion versus full range-of-motion training in the development of maximal upper-body strength in women. A 1 repetition maximum bench press was used as the criterion measurement. A 10-week, 2 days per week training regimen was used. Subjects were divided into 3 groups. Group 1 (n = 13) trained with 3 full range-of-motion sets on the bench press. Group 2 (n = 8) trained with 3 partial range-of-motion sets. Group 3 (n = 8), serving as a quasi-control, trained with an equal combination of partial and full range-of-motion sets. Findings indicated that each of the 3 groups experienced an increase in bench-press strength from pre- to posttest. In addition, a statistically significant difference was found between the full range-of-motion group and the partial and mixed groups (p < 0.5). This finding suggests that lifting through a full range of motion was superior to the other training regimens used in this study. However, this investigation also indicated that the partial technique had a positive effect on strength across time within the parameters of this study.

An analysis of full range of motion vs. partial range of motion training in the development of strength in untrained men.

The purpose of this investigation was to compare partial range of motion versus full range of motion training in the development of maximal strength. The bench press was used as the criterion measurement. The study was conducted over a 10-week period with training sessions occurring twice per week. Subjects were divided into 3 groups. Group 1 (N = 11) trained with 3 full range of motion sets on the bench press. Group 2 (N = 15) trained with 3 partial range of motion sets. A partial repetition was defined as one that is beyond the sticking point 2 to 5 inches from full extension of the elbows. Group 3 (N = 30) trained with a combination of partial and full range of motion sets. All subjects were pre- and posttested on the bench press through a full range of motion using a 1 repetition maximum. Each of the 3 groups demonstrated statistically significant increases in strength from pre- to posttest. No differences were found between groups. These findings appear to suggest that partial range of motion training can positively influence the development of maximal strength. Therefore, those involved in the strength and conditioning profession can confidently including this method as an adjunct to their normal training protocols when working with individuals similar to those found in this investigation. It is suggested that additional research be conducted to further establish the effectiveness of partial range of motion training in developing maximal strength.

Numerical studies of backscattering enhancement of electromagnetic waves from two-dimensional random rough surfaces with the forward-backward/novel spectral acceleration method.

The forward-backward method with a novel spectral acceleration algorithm (FB/NSA) has been shown to be a highly efficient O(Ntot) iterative method of moments, where Ntot is the total number of unknowns to be solved, for the computation of electromagnetic (EM) wave scattering from both one-dimensional and two-dimensional (2-D) rough surfaces. The efficiency of the method makes studies of backscattering enhancement from moderately rough impedance surfaces at large incident angles tractable. Variations in the characteristics of backscattering enhancement with incident angle, surface impedance, polarization, and surface statistics are investigated by use of the 2-D FB/NSA method combined with parallel computing techniques. The surfaces considered are Gaussian random processes with an isotropic Gaussian spectrum and root-mean-square surface heights and slopes ranging from 0.5 lambda to lambda and from 0.5 to 1.0, respectively, where lambda is the EM wavelength in free space. Incident angles ranging from normal incidence up to 70 degrees are considered in this study. It is found that backscattering enhancement depends strongly on all parameters of interest. America

Nasal T-cell lymphoma: case report and review of diagnostic features.

A 73-year-old man was referred to us for evaluation of extensive nasal crusting and progressive erosion of the nasal midline structures. Clinical examination suggested that the patient had a T-cell lymphoma, a suspicion that was confirmed on immunohistochemical analysis. The patient was treated with combination chemo- and radiotherapy and exhibited a marked response. At the 14-month followup, he remained disease-free.

Surgical treatment of squamous cell carcinoma of the base of tongue.

INTRODUCTION: Squamous cell carcinoma (SSC) of the tongue base has historically been shown to be associated with a poor prognosis. We reviewed our experience with primary surgery followed by postoperative radiation therapy (XRT) to determine the impact of our treatment protocols on outcome. METHODS: We retrospectively reviewed the records of all patients presenting to the University of Pittsburgh with previously untreated SSC of the tongue base between 1980-1997. Patients who were treated nonoperatively were excluded from analysis. Surgical excision of the primary was performed with ipsilateral neck dissection. The contralateral neck was dissected when the primary lesion was located in the midline or for clinically positive contralateral neck nodes. Postoperatively, most patients (93%) received XRT to the primary site and neck. Adjuvant chemotherapy was offered if histologic signs of aggressive behavior were identified (multiple nodes or extracapsular spread). RESULTS: Of 87 patients identified, 39 (45%) were initially seen with T1 or T2 tumors. Seventy-nine patients (91%) were initially seen with stage III or IV disease. Contralateral neck dissection was performed in 36 patients (41%). Metastatic disease was demonstrated in 84% of ipsilateral neck nodes and in 47% of contralateral neck nodes. Occult metastases were found in 61% of clinically N0 necks. Local recurrence occurred in 5 patients, regional recurrence occurred in 12 patients, and distant metastases developed in 22 patients. Overall and disease-specific survival rates at 5 years for all patients were 49% and 56%, respectively. The 5 year disease-specific survival rates for stage I, stage II, stage III, and stage IV disease were 100%, 86%, 62%, and 48%. The 5-year disease-specific survival rate was 88% for T1 lesions, 64% for T2 lesions, 58% for T3 lesions, and 30% for T4 lesions (p <.05, log-rank test). CONCLUSIONS: Surgical treatment of SCC of the tongue base is highly effective in achieving local disease control and disease-free survival for early lesions. Because both functional outcome and survival are poor after surgical treatment of advanced lesions, we now offer brachytherapy with XRT or participation in a combined chemoradiation protocol rather than primary surgical therapy to patients with advanced disease. Prospective studies are needed to compare the effect of these organ-preserving therapies with traditional combined surgery and XRT to determine the effect on functional outcome and quality of life.

Proposal of standardization on screening tests for detection of distant metastases from head and neck cancer.

A standardized approach to screening for distant metastases must be flexible. This reflects the fact that the issues involved have not been adequately studied to allow evidence-based recommendations. Effective and responsible application of screening for distant metastasis would improve our ability to council patients regarding important therapeutic decisions. It would also have important consequences on healthcare economics. Screening recommendations should reflect the stage of the primary tumor and the histologic cell type because these two parameters most clearly correlate with the risk for distant metastases. The most commonly encountered distant metastases are pulmonary. The most sensitive validated screening technique is just computed tomography (CT). Advanced technologies such as simultaneous positron emission tomography/CT may replace these prior technologies in the near future. Recommendations for routine screening following curative treatment are subjective at this time. Careful history and physical examination remains the basis for the follow-up evaluation. The sensitivity and cost effectiveness of imaging studies in this setting remains unstudied and contentious.

The role of topical antibiotic prophylaxis in patients undergoing contaminated head and neck surgery with flap reconstruction.

OBJECTIVES/HYPOTHESIS: Patients undergoing contaminated head and neck surgery with flap reconstruction have wound infection rates of 20% to 25% with parenteral antibiotic prophylaxis. Studies suggest that perioperative antimicrobial mouthwash reduces oropharyngeal flora and may prevent wound infections. We hypothesized that the addition of topical antibiotics to a parenteral prophylactic regimen would reduce the incidence of wound infection in these high-risk patients. STUDY DESIGN: We performed a randomized, prospective clinical trial. METHODS: Patients received either 1) parenteral piperacillin/tazobactam (3.375 g every 6 hours for 48 h) or 2) parenteral piperacillin/tazobactam plus topical piperacillin/tazobactam administered as a mouthwash immediately before surgery and once a day for 2 days postoperatively, with piperacillin/tazobactam added to the intraoperative irrigation solution. The wounds of all patients were evaluated daily using predefined objective criteria. RESULTS: Sixty-two patients met inclusion criteria and were enrolled in the study. The overall wound infection rate was 8.1% (95% confidence interval [CI], 2.7%-17.8%). Two of 31 patients (6.4%) who received parenteral antibiotics alone developed a wound infection compared with 3 of 31 patients (9.7%) randomly assigned to receive topical plus parenteral antibiotics. This difference was not statistically significant (P = >.05). Infection rate was not associated with flap type (rotational vs. free tissue transfer), mandibular reconstruction, age, gender, tumor site, stage, surgical duration, or blood loss. CONCLUSIONS: These results suggest that piperacillin/tazobactam is a highly effective antibiotic for prevention of wound infection in patients undergoing flap reconstruction following contaminated head and neck surgery. However, the addition of topical piperacillin/tazobactam does not appear to enhance the prophylactic benefit of parenteral antibiotics alone.

Prevention of radiation-induced mucositis.

Radiation-induced mucositis is an important dose-limiting acute side effect associated with the treatment of tumors of the upper aerodigestive tract. The toxicity of radiation therapy increases with prior or concurrent administration of some chemotherapeutic agents. Pretreatment eradication of infection, maintenance of oral hygiene, and treatment breaks, as necessary, have been the mainstay of the therapeutic options for patients with radiation-induced mucositis. Recent research has begun to clarify the pathophysiology of radiation-induced mucositis. This suggests that new, more effective agents for both prevention and treatment may be forthcoming in the near future. Currently, no highly effective and widely accepted prevention or treatment exists.