Most ovarian cancers are infiltrated by prognostically relevant activated T cells
, yet exhibit low response rates to immune checkpoint inhibitors
. Memory B cell and plasma cell infiltrates have ...previously been associated with better outcomes in ovarian cancer
, but the nature and functional relevance of these responses are controversial. Here, using 3 independent cohorts that in total comprise 534 patients with high-grade serous ovarian cancer, we show that robust, protective humoral responses are dominated by the production of polyclonal IgA, which binds to polymeric IgA receptors that are universally expressed on ovarian cancer cells. Notably, tumour B-cell-derived IgA redirects myeloid cells against extracellular oncogenic drivers, which causes tumour cell death. In addition, IgA transcytosis through malignant epithelial cells elicits transcriptional changes that antagonize the RAS pathway and sensitize tumour cells to cytolytic killing by T cells, which also contributes to hindering malignant progression. Thus, tumour-antigen-specific and -antigen-independent IgA responses antagonize the growth of ovarian cancer by governing coordinated tumour cell, T cell and B cell responses. These findings provide a platform for identifying targets that are spontaneously recognized by intratumoural B-cell-derived antibodies, and suggest that immunotherapies that augment B cell responses may be more effective than approaches that focus on T cells, particularly for malignancies that are resistant to checkpoint inhibitors.
This study aimed to test the role of hydrogen sulfide (H2S) in the responses regarding the nitric oxide- (NO) and sulfur (S)-mediated improvement in photosynthesis and growth under cadmium (Cd) ...stress in mustard (Brassica juncea L. cv. Giriraj), and integrate the mechanisms of S, nitrogen (N), and antioxidant metabolism. The plants grown with Cd (200 mg Cd kg−1 soil) exhibited reduced assimilation of S and N and diminished photosynthetic performance, which was associated with higher Cd accumulation-induced excess reactive oxygen species (ROS) production. The application of 100 μM of sodium nitroprusside (SNP, a NO donor) together with a more prominent concentration of S resulted in increased photosynthetic S- and N-use efficiency, production of non-protein thiols and phytochelatins, efficiency of enzymatic (superoxide dismutase, ascorbate peroxidase, and glutathione reductase), non-enzymatic antioxidants (ascorbate and glutathione) limiting Cd accumulation and, thus, reduced oxidative stress (superoxide radical, hydrogen peroxide, and thiobarbituric acid reactive species content). The benefit of NO together with S was manifested through a modulation in H2S production. The use of 100 μM of hypotaurine (HT; H2S scavenger) or 100 μM of cPTIO (2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide) in plants treated with NO plus S reversed the action of NO plus S, with a higher reduction in photosynthesis and growth with the use of HT, suggesting that H2S plays a significant role in the NO- and S-mediated alleviation of Cd stress. The interplay of NO and ES with H2S may be used in augmenting the photosynthesis and growth of Cd-grown mustard plants.
Hundreds of non-proteinogenic (np) amino acids (AA) are found in plants and can in principle enter human protein synthesis through foods. While aminoacyl-tRNA synthetase (AARS) editing potentially ...provides a mechanism to reject np AAs, some have pathological associations. Co-crystal structures show that vegetable-sourced azetidine-2-carboxylic acid (Aze), a dual mimic of proline and alanine, is activated by both human prolyl- and alanyl-tRNA synthetases. However, it inserts into proteins as proline, with toxic consequences in vivo. Thus, dual mimicry increases odds for mistranslation through evasion of one but not both tRNA synthetase editing systems.
The current study was undertaken with the objective of sire evaluation as well as studying the effect of genetic and non-genetic factors on growth performance in males of Tharparkar and Karan Fries ...Cattle. Data on body weights of Tharparkar and Karan Fries males born during the period 1994-2012 at ICAR-NDRI, Karnal, were utilized. The overall least squares means of birth weight and weights at one-month interval up to 12 months of age were 26.92±0.24, 35.55±0.22, 45.04±0.28, 57.56±0.40, 70.02±0.51, 82.62±0.66, 95.18±0.80, 105.11±1.55, 108.19±1.15, 114.20±1.15, 120.11±1.09, 130.35±1.11 and 136.91±4.13 kg respectively, in KF males. In TP males, least square means for birth and one-month were 21.34±0.77 and 25.63±0.67 kg, respectively. Effect of month and period of birth was highly significant on all traits except 1 month and 12-months for the former effect. The effects of genetic group and parity were mostly significant on body weights in KF males. Regression on birth weight was highly significant for all the weight traits. Effect of sire and birth-month was highly significant on all traits except one-month weight in KF. In Tharparkar, effect of season was highly significant on birth weight. Growth curves were linear, and deviations of average body weekly weight showed more divergence with increasing age. Growth rates from birth to three-months age in KF and TP males were 320 g/day and 226 g/day. Effect of non-genetic factors indicated the need of further improvement in feeding and management practices for augmenting growth, i.e. body weights especially in calves born to primiparous dams.
Titanium dioxide (TiO
) thin films were deposited on glass substrates at 350 °C using the spray pyrolysis technique. As deposited and annealed thin films were characterized by X-ray diffraction, ...scanning electron microscopy, UV-VIS spectroscopy, and photodetection. Unlike the as deposited samples which were amorphous, annealed samples show an anatase phase. Films were absorbent in the UV region and the band gap energy decreases from 3.78 eV to 3.4 eV with annealing. The photoresponse of TiO
photodetectors was recorded under UV (
= 365 nm,
= 254 nm) and visible light illumination by reversible switching (ON/OFF) cycles using DC electrical characterization. Photosensitive properties such as reproducible photosensitivity, responsivity, and detectivity were also studied.
To determine whether there is a difference in orthopaedic trauma patient medication satisfaction and adherence using an oral versus subcutaneous injectable anticoagulant for venous thromboembolism ...chemoprophylaxis.
Randomized controlled trial.
Single academic Level 1 trauma center.
One hundred twenty adult orthopaedic trauma patients with operative pelvic or lower extremity fractures were randomized and completed the study.
Three weeks of either the service standard 40 mg once daily enoxaparin versus trial medication 10 mg once daily rivaroxaban postoperatively.
Patient satisfaction as measured by the Treatment Satisfaction Questionnaire for Medication (TSQM-9). Medication adherence as measured by the Morisky Medication Adherence Scale (MMAS-8).
Medication adherence was similar in both groups. Medication satisfaction was significantly higher in the oral rivaroxaban group based on the TSQM-9 and patient-reported data. Secondary outcomes found no significant difference in the incidence of bleeding events or clinically relevant venous thromboembolism. The enoxaparin group experienced more adverse medication-related events. The rivaroxaban medication regimen costs 7.5-10× less out of pocket for uninsured patients.
The results of this randomized controlled trial demonstrate that patients with surgical orthopaedic trauma prefer an oral anticoagulant for postoperative venous thromboembolism chemoprophylaxis and suggest that rivaroxaban may be a viable option. Furthermore, large-scale studies are needed to confirm safety and efficacy for rivaroxaban in this population as a potential alternative to enoxaparin and aspirin.
Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.
Mg-doped ZnO (MZO) nanopowders were synthesized by sol-gel process. These samples are then characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM) and photoluminescence (PL) ...analyses. Resistive sensors based on Mg-doped ZnO thick layers deposited on alumina substrates equipped with platinum interdigitated electrodes were fabricated and used as UV-Vis light activated NO
2
sensors. The dark and illumination conditions are both utilized to perform NO
2
gas sensing tests by exposing the sensors to UV-Vis radiation (
λ
= 400 nm). Under irradiation condition, NO
2
detection with Mg-doped ZnO sensor could be successfully performed even to room temperature (30 °C). Furthermore, photoactivation also promoted NO
2
sensitivity and shortened the signal recovery of Mg-doped ZnO sensors compared to undoped one. Results demonstrated that Mg-doped ZnO might be promising sensing materials for the detection of NO
2
under UV-Vis illumination.
OBJECTIVE:To review the orthopaedic injuries from watercraft treated surgically at our institution and report the mechanisms, fractures, and complications encountered.
DESIGN:Retrospective case ...series.
SETTING:Level I trauma center.
PATIENTS/PARTICIPANTS:There were 216 fractures from watercraft in 146 patients. Average age was 33 years (range 4–78 years), there were 68% males (99/146), and 16% of the injuries occurred in children.
INTERVENTION:Operative fracture fixation.
MAIN OUTCOME MEASUREMENTS:After IRB approval, data were collected from January 1, 1998, to December 31, 2015, for patients including demographics, watercraft type, mechanism of injury, fracture pattern, infection, organisms, union, and amputation. Descriptive statistics were used.
RESULTS:There were 130 closed fractures (60%) and 86 open fractures (40%). There were 146 (67%) lower extremity injuries, 49 (23%) upper extremity injuries, and 21 (10%) pelvic injuries. The overall postoperative infection rate was 9% (20/216) and was commonly polymicrobial in nature. The postoperative infection rate in closed fractures was 4% (5/130) and the postoperative infection rate in open fractures was 17% (15/86). Open fractures also had a high proportion of nonunion (8%) and amputation (16%).
CONCLUSIONS:This is the largest reported series of orthopaedic injuries from watercraft. These injuries can be devastating in nature and difficult to manage, particularly when they are open (40%). There is a high rate of postoperative infection (17%), nonunion (8%), and amputation (16%) associated with open orthopaedic watercraft fractures.
LEVEL OF EVIDENCE:Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
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