Lower extremity and trunk sagittal plane coordination strategies and kinetic distribution during landing in males and females.

Force attenuation during landing requires coordinated motion of the ankle, knee, hip, and trunk, and strategies may differ between sexes. Sagittal plane coordination of the ankle/knee, knee/hip, and knee/trunk, and lower extremity and trunk kinematics and kinetics was compared throughout landing between 28 males and 28 females. Coordination was assessed with a modified vector coding technique and binning analysis. Total support moments (TSM), each joint's percent contribution, and timing of the TSM were compared. Females landed with less isolated knee flexion in the ankle/knee, knee/hip, and knee/trunk couplings, but more simultaneous ankle/knee flexion, less simultaneous knee flexion/hip extension, and more simultaneous trunk/knee flexion. Females landed with larger plantarflexion angles from 0-16% and smaller trunk flexion angles from 0-78%. In females, absolute TSM were larger from 0-6% and smaller from 42-100%, and normalized TSM were larger from 0-8% and 26-42%. Females had greater ankle contribution to the TSM from 14-15% and 29-35%, smaller absolute peak TSM, and the peak TSM occurred earlier. Females compensated for less isolated knee flexion with greater simultaneous ankle/knee flexion early in landing and knee/trunk flexion later in landing. Coordination and TSM differences may influence force attenuation strategies and have implications for knee injury disparity between sexes.

Lower extremity coordination strategies to mitigate dynamic knee valgus during landing in males and females.

Frontal and sagittal plane landing biomechanics differ between sexes but reported values don't account for simultaneous segment or joint motion necessary for a coordinated landing. Frontal and sagittal plane coordination patterns, angles, and moments were compared between 28 males and 28 females throughout the landing phase of a drop vertical jump. Females landed with less isolated thigh abduction (p = 0.018), more in-phase motion (p < 0.001), and more isolated shank adduction (p = 0.028) between the thigh and shank in the frontal plane compared with males. Females landed with less in-phase (p = 0.012) and more anti-phase motion (p = 0.019) between the thigh and shank in the sagittal plane compared with males. Females landed with less isolated knee flexion (p = 0.001) and more anti-phase motion (p < 0.001) between the sagittal and frontal plane knee coupling compared with males. Waveform and discrete metric analyses revealed females land with less thigh abduction from 20 % to 100 % and more shank abduction from 0 to 100 % of landing, smaller knee adduction at initial contact (p = 0.002), greater peak knee abduction angles (p = 0.015), smaller knee flexion angles at initial contact (p = 0.035) and peak (p = 0.034), greater peak knee abduction moments (p = 0.024), greater knee abduction angles from 0 to 13 % and 19 to 30 %, greater knee abduction moments from 19 to 25 %, and smaller knee flexion moments from 3 to 5 % of landing compared with males. Females utilize greater frontal plane motion compared with males, which may be due to different inter-segmental joint coordination and smaller sagittal plane angles. Larger knee abduction angles and greater knee adduction motion in females are due to aberrant shank abduction rather than thigh adduction.

Implementing and evaluating a high-resolution diode array for patient-specific quality assurance of robotic brain stereotactic radiosurgery/radiotherapy.

The purpose of the study was to introduce and evaluate a high-resolution diode array for patient-specific quality assurance (PSQA) of CyberKnife brain stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT). Thirty-three intracranial plans were retrospectively delivered on the SRS MapCHECK using fixed cone, Iris, and multileaf collimator (MLC). The plans were selected to cover a range of sites from large tumor bed, single/multiple small brain metastases (METs) to trigeminal neuralgia. Fiducial tracking using the four fiducials embedded around the detector plane was used as image guidance. Results were analyzed before and after registration based on absolute dose gamma criterion of 1 mm distance-to-agreement and 0.5%-3% dose-difference. Overall, the gamma passing rates (1 mm and 3% criterion) before registration for all the patients were above 90% for all three treatment modalities (96.8 ± 3.5%, the lowest passing rate of 90.4%), and were improved after registration (99.3 ± 1.5%). When tighter criteria (1 mm and 2%) were applied, the gamma passing rates after registration for all the cases dropped to 97.3 ± 3.2%. For trigeminal neuralgia cases, we applied 1 mm and 0.5% criterion and the passing rates dropped from 100 ± 0.0% to 98.5 ± 2.0%. The mean delivery time was 33.4 ± 11.7 min, 24.0 ± 4.9 min, and 17.1 ± 2.6 min for the fixed cone, Iris, and MLC, respectively. With superior gamma passing rates and reasonable quality assurance (QA) time, we believe the SRS MapCHECK could be a good option for routine PSQA for CyberKnife SRS/SRT.

Hip and Knee Kinetics During a Back Squat and Deadlift.

ABSTRACT: Choe, KH, Coburn, JW, Costa, PB, and Pamukoff, DN. Hip and knee kinetics during a back-squat and deadlift. J Strength Cond Res 35(5): 1364-1371, 2021-The back-squat and deadlift are performed to improve hip and knee extensor function. The purpose of this study was to compare lower extremity joint kinetics (peak net joint moments [NJMs] and positive joint work [PJW]) between the back-squat and deadlift. Twenty-eight resistance-trained subjects (17 men: 23.7 ± 4.3 years, 1.76 ± 0.09 m, 78.11 ± 10.91 kg; 11 women: 23.0 ± 1.9 years, 1.66 ± 0.06 m, 65.36 ± 7.84 kg) were recruited. One repetition maximum (1RM) testing and biomechanical analyses occurred on separate days. Three-dimensional biomechanics of the back-squat and deadlift were recorded at 70 and 85% 1RM for each exercise. The deadlift demonstrated larger hip extensor NJM than the back-squat {3.59 (95% confidence interval [CI]: 3.30-3.88) vs. 2.98 (95% CI: 2.72-3.23) Nm·kg-1, d = 0.81, p < 0.001}. However, the back-squat had a larger knee extensor NJM compared with the deadlift (2.14 [95% CI: 1.88-2.40] vs. 1.18 [95% CI: 0.99-1.37] Nm·kg-1, d = 1.44 p < 0.001). More knee PJW was performed during the back-squat compared with the deadlift (1.85 [95% CI: 1.60-2.09] vs. 0.46 [95% CI: 0.35-0.58] J·kg-1, d = 2.10, p < 0.001). However, there was more hip PJW during the deadlift compared with the back-squat (3.22 [95% CI: 2.97-3.47] vs. 2.37 [95% CI: 2.21-2.54] J·kg-1, d = 1.30, p < 0.001). Larger hip extensor NJM and PJW during the deadlift suggest that individuals targeting their hip extensors may yield greater benefit from the deadlift compared with the back-squat. However, larger knee extensor NJM and PJW during the back-squat suggest that individuals targeting their knee extensor muscles may benefit from incorporating the back-squat compared with the deadlift.

Improved outcomes after radiotherapy for prostate cancer: Anticoagulation, antiplatelet therapy, and platelet count as key factors in disease progression.

BACKGROUND: Several studies have suggested that antiplatelet (AP) or anticoagulant (AC) therapy may improve outcome in men with prostate cancer. We evaluated the effects of AP/AC therapy and tested the hypothesis that platelet count may also be associated with outcomes. METHODS: A total of 482 patients received primary radiotherapy (median dose 72 Gy) for nonmetastatic prostate cancer; 49% received androgen deprivation therapy. NCCN risk was low/intermediate/high risk in 39%/39%/22%. AP/AC therapy and platelet counts were analyzed with respect to freedom from biochemical failure (FFBF, nadir+2), distant metastasis (FFDM), and cause specific survival (CSS). RESULTS: After a median follow-up of 103 months, 10-year FFBF, FFDM, and CSS were 77%, 92%, and 96%, respectively. The 10-year cumulative incidence of BF and DM (with death as a competing event) was 19% and 7.0%, respectively. The 32% of men on AP/AC therapy had a lower incidence of 10-year BF (P = .016) and a trend toward a lower incidence of DM (P = .084) and CSS (P = .091). In the entire cohort, lowest platelet quartile (platelet count <187) was associated with higher 10-year BF (31% vs 16%, P = .0042) but not DM (9.4% vs 5.2%, P = .22) nor CSS (P = .76) compared with those patients with platelet count ≥187. AP/AC therapy was associated with a larger absolute reduction in BF for men with lowest platelet quartile (10-year BF of 21% vs 38%, P = .092) vs platelet ≥187 (10-year BF of 10% vs 18%, P = .053). Lowest platelet quartile remained associated with higher BF and DM on multivariable analysis controlling for risk category, WBC, and Hg. CONCLUSION: AP/AC was associated with improved FFBF. Low platelet count was associated with inferior FFBF and FFDM after prostate radiotherapy. This association was tempered when antiplatelet and anticoagulant therapy was administered.

Phase II trial of hippocampal-sparing whole brain irradiation with simultaneous integrated boost for metastatic cancer.

BACKGROUND: Advanced radiotherapeutic treatment techniques limit the cognitive morbidity associated with whole-brain radiotherapy (WBRT) for brain metastasis through avoidance of hippocampal structures. However, achieving durable intracranial control remains challenging. METHODS: We conducted a single-institution single-arm phase II trial of hippocampal-sparing whole brain irradiation with simultaneous integrated boost (HSIB-WBRT) to metastatic deposits in adult patients with brain metastasis. Radiation therapy consisted of intensity-modulated radiation therapy delivering 20 Gy in 10 fractions over 2-2.5 weeks to the whole brain with a simultaneous integrated boost of 40 Gy in 10 fractions to metastatic lesions. Hippocampal regions were limited to 16 Gy. Cognitive performance and cancer outcomes were evaluated. RESULTS: A total of 50 patients, median age 60 years (interquartile range, 54-65), were enrolled. Median progression-free survival was 2.9 months (95% CI: 1.5-4.0) and overall survival was 9 months. As expected, poor survival and end-of-life considerations resulted in a high exclusion rate from cognitive testing. Nevertheless, mean decline in Hopkins Verbal Learning Test-Revised delayed recall (HVLT-R DR) at 3 months after HSIB-WBRT was only 10.6% (95% CI: -36.5‒15.3%). Cumulative incidence of local and intracranial failure with death as a competing risk was 8.8% (95% CI: 2.7‒19.6%) and 21.3% (95% CI: 10.7‒34.2%) at 1 year, respectively. Three grade 3 toxicities consisting of nausea, vomiting, and necrosis or headache were observed in 3 patients. Scores on the Multidimensional Fatigue Inventory 20 remained stable for evaluable patients at 3 months. CONCLUSIONS: HVLT-R DR after HSIB-WBRT was significantly improved compared with historical outcomes in patients treated with traditional WBRT, while achieving intracranial control similar to patients treated with WBRT plus stereotactic radiosurgery (SRS). This technique can be considered in select patients with multiple brain metastases who cannot otherwise receive SRS.

Decrease of Protease-Resistant PrPSc Level in ScN2a Cells by Polyornithine and Polyhistidine.

Based on previous studies reporting the anti-prion activity of poly-L-lysine and poly-L-arginine, we investigated cationic poly-L-ornithine (PLO), poly-L-histidine (PLH), anionic poly-L-glutamic acid (PLE) and uncharged poly-L-threonine (PLT) in cultured cells chronically infected by prions to determine their anti-prion efficacy. While PLE and PLT did not alter the level of PrPSc, PLO and PLH exhibited potent PrPSc inhibition in ScN2a cells. These results suggest that the anti-prion activity of poly-basic amino acids is correlated with the cationicity of their functional groups. Comparison of anti-prion activity of PLO and PLH proposes that the anti-prion activity of poly-basic amino acids is associated with their acidic cellular compartments.

Application of Centrifugal Partition Chromatography for Bioactivity-Guided Purification of Antioxidant-Response-Element-Inducing Constituents from Atractylodis Rhizoma Alba.

Activity-guided separation of antioxidant response element (ARE)-inducing constituents from the rhizomes of Atractylodis Rhizoma Alba was performed by the combination of centrifugal partition chromatography (CPC) and an ARE luciferase reporter assay. From 3 g of the active n-hexane fraction, one polyacetylene, (6E,12E)-tetradeca-6,12-dien-8,10-diyne-1,3-diyl diacetate (47.3 mg), and two sesquiterpenes, atractylenolide I (40.9 mg), and selina-4(14),7(11)-dien-8-one (6.0 mg) were successfully isolated by CPC with n-hexane⁻ethyl acetate⁻methanol⁻water (8:2:8:2, v/v). The chemical structures of the isolated compounds were determined by ¹H- and 13C-NMR and ESI-MS. Among the isolated compounds, (6E,12E)-tetradeca-6,12-diene-8,10-diyne-1,3-diol diacetate and selina-4(14),7(11)-dien-8-one increased ARE activity 32.9-fold and 16.6-fold, respectively, without significant cytotoxicity, when 5 µM sulforaphane enhanced ARE activity 27.1-fold. However, atractylenolide I did not increase ARE activity at 100 µM, and showed cytotoxicity at concentrations over 10 µM.

Bilateral Alterations in Running Mechanics and Quadriceps Function Following Unilateral Anterior Cruciate Ligament Reconstruction.

BACKGROUND: Following anterior cruciate ligament reconstruction (ACLR), individuals have quadriceps muscle impairments that influence gait mechanics and may contribute to an elevated risk of knee osteoarthritis. OBJECTIVES: To compare running mechanics and quadriceps function between individuals who have undergone ACLR and those in a control group, and to evaluate the association between quadriceps function and running mechanics. METHODS: In this controlled, cross-sectional laboratory study, 38 individuals who previously underwent primary unilateral ACLR (mean ± SD time since reconstruction, 48.0 ± 25.0 months) were matched to 38 control participants based on age, sex, and body mass index, and underwent assessments of quadriceps muscle performance and running biomechanics. Quadriceps muscle performance was assessed via isokinetic and isometric knee extension peak torque and rate of torque development (RTD) over 2 time frames: 0 to 100 milliseconds (RTD100) and 0 to 200 milliseconds (RTD200). Running evaluation included assessment of the knee flexion angle (KFA), knee extension moment (KEM), rate of knee extension moment (RKEM), vertical instantaneous loading rate, and vertical impact peak. RESULTS: On average, there was a smaller KFA (P = .016) in the involved limb compared to the uninvolved limb in the ACLR group. Compared to limbs in the control group, involved limbs in the ACLR group had lower RTD100 (P = .015), lower peak torque at 60°/s (P = .007), lower peak torque at 180°/s (P = .016), smaller KFA (P<.001), lower KEM (P = .001), lower RKEM (P = .004), and higher vertical instantaneous loading rate (P = .016). Compared to limbs in the control group, uninvolved limbs in the ACLR group had lower RTD100 (P = .003), lower peak torque at 60°/s (P = .017), and smaller KFA (P = .01). For the involved limbs in the ACLR group, there was a low correlation between isokinetic peak torque at 180°/s and RKEM (r = 0.38, P = .01), and a negligible correlation between RTD100 and RKEM (r = 0.26, P<.05). No differences were found in isometric strength for any comparison. CONCLUSION: Individuals who have undergone ACLR have bilateral alterations in running mechanics that are weakly associated with diminished quadriceps muscle performance. J Orthop Sports Phys Ther 2018;48(12):960-967. Epub 22 Jul 2018. doi:10.2519/jospt.2018.8170.

Effect of Whole-Body Vibration on Sagittal Plane Running Mechanics in Individuals With Anterior Cruciate Ligament Reconstruction: A Randomized Crossover Trial.

OBJECTIVE: To examine the effect of whole-body vibration (WBV) on running biomechanics in individuals with anterior cruciate ligament reconstruction (ACLR). DESIGN: Single-blind randomized crossover trial. SETTING: Research laboratory. PARTICIPANTS: Individuals (N=20) with unilateral ACLR (age [± SD]=22.3 [±3.3] years; mass=71.8 [±15.3] kg; time since ACLR=44.9 [±22.8] months; 15 females, 10 patellar tendon autograft, 7 hamstrings autograft, 3 allograft; International Knee Documentation Committee Score=83.5 [±9.3]). MAIN OUTCOME MEASURE: Participants performed isometric squats while being exposed to WBV or no vibration (control). WBV and control conditions were delivered in a randomized order during separate visits separated by 1-week washout periods. Running biomechanics of the injured and uninjured limbs were evaluated before and immediately after each intervention. Dependent variables included peak vertical ground reaction force (GRF) and loading rate (LR), peak knee flexion angle and external moment, and knee flexion excursion during the stance phase of running. RESULTS: There was an increase in knee flexion excursion (+4.1°, 95% confidence interval [CI]: 0.65, 7.5°) and a trend toward a reduction in instantaneous LR after WBV in the injured limb (-4.03 BW/sec-1, 95% CI -0.38, -7.69). No effect was observed on peak GRF, peak knee flexion angle, or peak external knee flexion moment, and no effect was observed in the uninjured limb. CONCLUSIONS: Our findings indicate that a single session of WBV acutely increases knee flexion excursion. WBV could be useful to improve running characteristics in individuals with knee pathology.

Review on a Traditional Herbal Medicine, Eurycoma longifolia Jack (Tongkat Ali): Its Traditional Uses, Chemistry, Evidence-Based Pharmacology and Toxicology.

Eurycoma longifolia Jack (known as tongkat ali), a popular traditional herbal medicine, is a flowering plant of the family Simaroubaceae, native to Indonesia, Malaysia, Vietnam and also Cambodia, Myanmar, Laos and Thailand. E. longifolia, is one of the well-known folk medicines for aphrodisiac effects as well as intermittent fever (malaria) in Asia. Decoctions of E. longifolia leaves are used for washing itches, while its fruits are used in curing dysentery. Its bark is mostly used as a vermifuge, while the taproots are used to treat high blood pressure, and the root bark is used for the treatment of diarrhea and fever. Mostly, the roots extract of E. longifolia are used as folk medicine for sexual dysfunction, aging, malaria, cancer, diabetes, anxiety, aches, constipation, exercise recovery, fever, increased energy, increased strength, leukemia, osteoporosis, stress, syphilis and glandular swelling. The roots are also used as an aphrodisiac, antibiotic, appetite stimulant and health supplement. The plant is reported to be rich in various classes of bioactive compounds such as quassinoids, canthin-6-one alkaloids, ß-carboline alkaloids, triterpene tirucallane type, squalene derivatives and biphenyl neolignan, eurycolactone, laurycolactone, and eurycomalactone, and bioactive steroids. Among these phytoconstituents, quassinoids account for a major portion of the E. longifolia root phytochemicals. An acute toxicity study has found that the oral Lethal Dose 50 (LD50) of the alcoholic extract of E. longifolia in mice is between 1500-2000 mg/kg, while the oral LD50 of the aqueous extract form is more than 3000 mg/kg. Liver and renal function tests showed no adverse changes at normal daily dose and chronic use of E. longifolia. Based on established literature on health benefits of E. longifolia, it is important to focus attention on its more active constituents and the constituents' identification, determination, further development and most importantly, the standardization. Besides the available data, more evidence is required regarding its therapeutic efficacy and safety, so it can be considered a rich herbal source of new drug candidates. It is very important to conserve this valuable medicinal plant for the health benefit of future generations.

Pre-treatment factors associated with detecting additional brain metastases at stereotactic radiosurgery.

The number of brain metastases identified on diagnostic magnetic resonance imaging (MRI) is a key factor in consideration of stereotactic radiosurgery (SRS). However, additional lesions are often detected on high-resolution SRS-planning MRI. We investigated pre-treatment clinical characteristics that are associated with finding additional metastases at SRS. Patients treated with SRS for brain metastases between the years of 2009-2014 comprised the study cohort. All patients underwent frame-fixed, 1 mm thick MRI on the day of SRS. Patient, tumor, and treatment characteristics were analyzed for an association with increase in number of metastases identified on SRS-planning MRI. 289 consecutive SRS cases were analyzed. 725 metastases were identified on pre-treatment MRI and 1062 metastases were identified on SRS-planning MRI. An increase in the number of metastases occurred in 34 % of the cases. On univariate analysis, more than four metastases and the diameter of the largest lesion were significantly associated with an increase in number of metastases on SRS-planning MRI. When stratified by the diameter of the largest lesion into <2, 2-3, or ≥3 cm, additional metastases were identified in 37, 29, and 18 %, respectively. While this increase in the number of metastases is largely due to the difference in imaging technique, the number and size of the metastases were also associated with finding additional lesions. These clinical factors may be considered when determining treatment options for brain metastases.

An integrative somatic mutation analysis to identify pathways linked with survival outcomes across 19 cancer types.

MOTIVATION: Identification of altered pathways that are clinically relevant across human cancers is a key challenge in cancer genomics. Precise identification and understanding of these altered pathways may provide novel insights into patient stratification, therapeutic strategies and the development of new drugs. However, a challenge remains in accurately identifying pathways altered by somatic mutations across human cancers, due to the diverse mutation spectrum. We developed an innovative approach to integrate somatic mutation data with gene networks and pathways, in order to identify pathways altered by somatic mutations across cancers. RESULTS: We applied our approach to The Cancer Genome Atlas (TCGA) dataset of somatic mutations in 4790 cancer patients with 19 different types of tumors. Our analysis identified cancer-type-specific altered pathways enriched with known cancer-relevant genes and targets of currently available drugs. To investigate the clinical significance of these altered pathways, we performed consensus clustering for patient stratification using member genes in the altered pathways coupled with gene expression datasets from 4870 patients from TCGA, and multiple independent cohorts confirmed that the altered pathways could be used to stratify patients into subgroups with significantly different clinical outcomes. Of particular significance, certain patient subpopulations with poor prognosis were identified because they had specific altered pathways for which there are available targeted therapies. These findings could be used to tailor and intensify therapy in these patients, for whom current therapy is suboptimal. AVAILABILITY AND IMPLEMENTATION: The code is available at: http://www.taehyunlab.org CONTACT: jhcheong@yuhs.ac or taehyun.hwang@utsouthwestern.edu or taehyun.cs@gmail.com SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

In Vitro Evaluation of the Effects of Eurycoma longifolia Extract on CYP-Mediated Drug Metabolism.

Eurycoma longifolia (Simaroubaceae) is a popular folk medicine that has traditionally been used in Southeast Asia as an antimalarial, aphrodisiac, antidiabetic, and antimicrobial and in antipyretic remedies. This study evaluates the effects of Eurycoma longifolia extract on cytochrome P450 (CYP) enzyme-mediated drug metabolism to predict the potential for herb-drug interactions. Methanolic extract of E. longifolia root was tested at concentrations of 1, 3, 10, 30, 100, 300, and 1000 µg/mL in human liver microsomes or individual recombinant CYP isozymes. The CYP inhibitory activity was measured using the cocktail probe assay based on liquid chromatography-tandem mass spectrometry. E. longifolia showed weak, concentration-dependent inhibition of CYP1A2, CYP2A6, and CYP2C19. The inhibitory effects on these CYP isozymes were further tested using individual recombinant CYP isozymes, showing IC50 values of 324.9, 797.1, and 562.9 µg/mL, respectively. In conclusion, E. longifolia slightly inhibited the metabolic activities of CYP1A2, CYP2A6, and CYP2C19 but this issue requires careful attention in taking herbal medicines or dietary supplements containing E. longifolia extracts.

Role for a Zinc Finger Protein (Zfp111) in Transformation of 208F Rat Fibroblasts by Jaagsiekte Sheep Retrovirus Envelope Protein.

UNLABELLED: The native envelope gene (env) of Jaagsiekte sheep retrovirus (JSRV) also acts as an oncogene. To investigate the mechanism of transformation, we performed yeast 2-hybrid screening for cellular proteins that interact with Env. Among several candidates, we identified mouse or rat zinc finger protein 111 (zfp111). The interaction between Env and Zfp111 was confirmed through in vivo coimmunoprecipitation assays. Knockdown of endogenous Zfp111 caused a decrease in cell transformation by JSRV Env, while overexpression of Zfp111 increased overall Env transformation, supporting a role for Zfp111 in Env transformation. Knockdown of Zfp111 had no effect on the growth rate of parental rat 208F cells, while it decreased the proliferation rate of JSRV-transformed 208F cells, suggesting that JSRV-transformed cells became dependent on Zfp111. In addition, Zfp111 preferentially bound to a higher-mobility form of JSRV Env that has not been described previously. The higher-mobility form of Env (P70(env)) was found exclusively in the nuclear fraction, and size of its polypeptide backbone was the same as that of the cytoplasmic Env polyprotein (Pr80(env)). The differences in glycosylation between the two versions of Env were characterized. These results identify a novel cellular protein, Zfp111, that binds to the JSRV Env protein, and this binding plays a role in Env transformation. These results indicate that JSRV transformation also involves proteins and interactions in the nucleus. IMPORTANCE: The envelope protein (Env) of Jaagsiekte sheep retrovirus (JSRV) is an oncogene, but its mechanism of cell transformation is still unclear. Here we identified seven candidate cellular proteins that can interact with JSRV Env by yeast two-hybrid screening. This study focused on one of the seven candidates, zinc finger protein 111 (Zfp111). Zfp111 was shown to interact with JSRV Env in cells and to be involved in JSRV transformation. Moreover, coexpression of JSRV Env and Zfp111 led to the identification of a novel nuclear form of the JSRV Env protein that binds Zfp111. Nuclear Env was found to differ by glycosylation from the cytoplasmic Env precursor to the virion envelope proteins. These results suggest that JSRV Env transformation may involve nuclear events such as an alteration in transcription mediated by Env-Zfp111 interactions.

Atypical Meningiomas: Recurrence, Reoperation, and Radiotherapy.

INTRODUCTION: Atypical meningiomas (World Health Organization [WHO] grade II) represent a therapeutic challenge given their high recurrence rate and greater mortality compared with WHO grade I meningiomas. Traditionally, treatment has entailed attempts at gross total resection with radiation therapy reserved for residual disease or recurrences. METHODS: We retrospectively reviewed our patient database of atypical meningioma (AM) patients over the past 10 years to assess surgical and radiotherapeutic treatments administered, treatment-related complications, radiographic-clinical progression after treatment, and mortality. We identified 45 patients with AMs and excluded 2 patients with incomplete hospital records. RESULTS: The average age of our patients was 59.7 years. Forty-three AM patients underwent a total of 62 surgeries. Thirty patients underwent one initial surgical resection; 8 patients underwent a second resection for recurrence; 4 patients underwent 3 resections; and 1 patient underwent 4 resections for recurrences. The rate of postoperative complication was 12.9% (8/62). Five patients had postoperative wound infections requiring treatment, and 1 patient had a postoperative hematoma requiring surgical evacuation. There was 1 case of wound breakdown in a patient with a previously irradiated scalp and 1 case of lower-extremity venous thrombosis. Clinical follow-up ranged from 11-120 months with average follow-up of 43 months and median follow-up of 65 months. Nineteen patients (44%) developed clinical-radiographic evidence of recurrence at an average of 32.4 months after surgical resection. Of the recurrences, 12 were treated with repeat surgery and radiation therapy, 3 were treated with radiation therapy alone, and 2 with surgery alone. Radiation therapy included Gamma Knife (GK), CyberKnife (CK), intensity-modulated radiation therapy (IMRT), or some combination of these. There was one case of symptomatic radiation necrosis (1/15 or 6.6%). The survival rate at last follow-up of our patient cohort was 95.3%. CONCLUSIONS: Given their high rates of recurrence, AMs require close clinical follow-up and an individualized treatment strategy. Reoperation, radiotherapy, or combination therapy can be effective strategies at managing disease progression while minimizing treatment-related morbidity. Treatment planning that attempts to anticipate future therapies in the form of further surgery or radiotherapy may improve clinical outcomes in these patients. Seventeen patients underwent adjuvant radiation therapy: 7 patients with intensity-modulated radiation therapy (IMRT), 4 patients with Gamma Knife (GK), and 2 with CyberKnife (CK). Four patients underwent multiple treatments.

Proton T2 measurement and quantification of lactate in brain tumors by MRS at 3 Tesla in vivo.

PURPOSE: To evaluate the T2 relaxation time of lactate (Lac) in brain tumors and the correlation of the T2 and concentration with tumor grades. METHODS: Eight pairs of the subecho time sets of point-resolved spectroscopy were selected between 58 and 268 ms, with numerical and phantom analyses, for Lac T2 measurement. In vivo spectra were acquired from 24 subjects with gliomas (13 low grade and 11 high grade) and analyzed with LCModel using numerically-calculated basis spectra. The metabolite T2 relaxation time was obtained from monoexponential fitting of the multi-echo time (TE) signal estimates versus TE. The metabolite concentration was estimated from the zero-TE extrapolation of the T2 fits. RESULTS: The Lac T2 was estimated to be approximately 240 ms, without a significant difference between low and high grade tumors. The Lac concentration was estimated to be 4.1 ± 3.4 and 7.0 ± 4.7 mM for low and high grades respectively, but the difference was not significant. CONCLUSION: The Lac T2 was similar among gliomas regardless of their tumor grades. This suggests that the T2 value from this study may be applicable to obtain the T2 relaxation-free estimates of Lac in a subset of brain tumors.

Interactions between herbs and antidiabetics: an overview of the mechanisms, evidence, importance, and management.

Complementary and alternative therapies are quickly gaining importance because they are perceived to be free of side effects due to their natural origin. However, herbal remedies are complex mixtures of bioactive entities, which may interact with prescription drugs through pharmacokinetic or pharmacodynamic mechanisms and sometimes result in life-threatening consequences. In particular, diabetes patients are often treated with multiple medications due to different comorbidities, and such patients use antidiabetic medications for their entire lives; thus, it is important to make the public aware of herb interactions with antidiabetic drugs. In this paper, we summarize the reports available on the interaction of herbal remedies with oral hypoglycemic agents and describe mechanisms, preclinical or clinical evidence, importance, and management strategies.

A retrospective analysis of tumor volumetric responses to five-fraction stereotactic radiotherapy for paragangliomas of the head and neck (glomus tumors).

BACKGROUND: Skull base paragangliomas (SBP) are locally expansile tumors that can be treated with stereotactic radiotherapy with favorable results. This report describes the results of 31 patients with SBP treated with CyberKnife radiotherapy delivering a total dose of 25 Gray in five fractions. METHODS: All patients treated with five-fraction CyberKnife radiotherapy at a single institution were identified between 2007 and 2013. Tumor volumetric analyses were performed to assess responses to radiotherapy. RESULTS: Median follow-up was 24 months with a range of 4-78 months. Local control and overall survival were 100%. Of the 20 patients who presented with tinnitus, 12 reported improvement (60%), of whom 6 reported complete resolution. There was a 37.3% reduction in tumor volume among all patients (p = 0.16). On subset analysis of patients with ≥24 months of follow-up, tumor volume decreased 49% (p = 0.01). The rate of grade 1-2 toxicity was 19%, with no grade 3 or worse toxicity. CONCLUSION: A five-fraction CyberKnife-based stereotactic radiotherapy approach is safe and efficacious for the management for patients with SBP. Our findings suggest the potential use of this strategy as a definitive or salvage treatment option for SBP.