Fat embolism syndrome: A severe case diagnosed early using dual-energy CT and saved with VA-ECMO and inhaled nitric oxide.

Diagnosing FES is difficult and time-consuming, and identify FES as an etiology of right ventricular volume overload for early diagnosis. Because FES is a reversible condition, even severe cases can bse treated if the patient survives the acute phase.

Zaxinone mimics (MiZax) efficiently promote growth and production of potato and strawberry plants under desert climate conditions.

Climate changes and the rapid expanding human population have become critical concerns for global food security. One of the promising solutions is the employment of plant growth regulators (PGRs) for increasing crop yield and overcoming adverse growth conditions, such as desert climate. Recently, the apocarotenoid zaxinone and its two mimics (MiZax3 and MiZax5) have shown a promising growth-promoting activity in cereals and vegetable crops under greenhouse and field conditions. Herein, we further investigated the effect of MiZax3 and MiZax5, at different concentrations (5 and 10 µM in 2021; 2.5 and 5 µM in 2022), on the growth and yield of the two valuable vegetable crops, potato and strawberry, in the Kingdom of Saudi of Arabia. Application of both MiZax significantly increased plant agronomic traits, yield components and total yield, in five independent field trials from 2021 to 2022. Remarkably, the amount of applied MiZax was far less than humic acid, a widely applied commercial compound used here for comparison. Hence, our results indicate that MiZax are very promising PGRs that can be applied to promote the growth and yield of vegetable crops even under desert conditions and at relatively low concentrations.

New Series of Zaxinone Mimics (MiZax) for Fundamental and Applied Research.

The apocarotenoid zaxinone is a recently discovered regulatory metabolite required for proper rice growth and development. In addition, zaxinone and its two mimics (MiZax3 and MiZax5) were shown to have a remarkable growth-promoting activity on crops and a capability to reduce infestation by the root parasitic plant Striga through decreasing strigolactone (SL) production, suggesting their potential for application in agriculture and horticulture. In the present study, we developed a new series of MiZax via structural modification of the two potent zaxinone mimics (MiZax3 and MiZax5) and evaluated their effect on plant growth and Striga infestation. In general, the structural modifications to MiZax3 and MiZax5 did not additionally improve their overall performance but caused an increase in certain activities. In conclusion, MiZax5 and especially MiZax3 remain the likely most efficient zaxinone mimics for controlling Striga infestation.

Pacemaker implantation for persistent sinus node dysfunction in a patient with COVID-19.

A 46-year-old woman was admitted with coronavirus disease-2019 infection. Symptomatic sinus bradycardia occurred, followed by congestive heart failure. Therapeutics such as isoproterenol, theophylline, and cilostazol could not safely improve her symptoms. She underwent pacemaker implantation 53 days after admission. Atrial pacing remained was at 60% after 6 months.

Chemical genetic screening identifies nalacin as an inhibitor of GH3 amido synthetase for auxin conjugation.

Auxin inactivation is critical for plant growth and development. To develop plant growth regulators functioning in auxin inactivation pathway, we performed a phenotype-based chemical screen in Arabidopsis and identified a chemical, nalacin, that partially mimicked the effects of auxin. Genetic, pharmacological, and biochemical approaches demonstrated that nalacin exerts its auxin-like activities by inhibiting indole-3-acetic acid (IAA) conjugation that is mediated by Gretchen Hagen 3 (GH3) acyl acid amido synthetases. The crystal structure of Arabidopsis GH3.6 in complex with D4 (a derivative of nalacin) together with docking simulation analysis revealed the molecular basis of the inhibition of group II GH3 by nalacin. Sequence alignment analysis indicated broad bioactivities of nalacin and D4 as inhibitors of GH3s in vascular plants, which were confirmed, at least, in tomato and rice. In summary, our work identifies nalacin as a potent inhibitor of IAA conjugation mediated by group II GH3 that plays versatile roles in hormone-regulated plant development and has potential applications in both basic research and agriculture.

Evaluation of the Biostimulant Activity of Zaxinone Mimics (MiZax) in Crop Plants.

Global food security is a critical concern that needs practical solutions to feed the expanding human population. A promising approach is the employment of biostimulants to increase crop production. Biostimulants include compounds that boost plant growth. Recently, mimics of zaxinone (MiZax) were shown to have a promising growth-promoting effect in rice (Oryza sativa). In this study, we investigated the effect of MiZax on the growth and yield of three dicot horticultural plants, namely, tomato (Solanum lycopersicum), capsicum (Capsicum annuum), and squash (Cucurbita pepo) in different growth environments, as well as on the growth and development of the monocot date palm (Phoenix dactylifera), an important crop in the Middle East. The application of MiZax significantly enhanced plant height, flower, and branch numbers, fruit size, and total fruit yield in independent field trials from 2020 to 2021. Importantly, the amount of applied MiZax was far less than that used with the commercial compound humic acid, a widely used biostimulant in horticulture. Our results indicate that MiZax have significant application potential to improve the performance and productivity of horticultural crops.

Striga hermonthica Suicidal Germination Activity of Potent Strigolactone Analogs: Evaluation from Laboratory Bioassays to Field Trials.

The obligate hemiparasite Striga hermonthica is one of the major global biotic threats to agriculture in sub-Saharan Africa, causing severe yield losses of cereals. The germination of Striga seeds relies on host-released signaling molecules, mainly strigolactones (SLs). This dependency opens up the possibility of deploying SL analogs as "suicidal germination agents" to reduce the accumulated seed bank of Striga in infested soils. Although several synthetic SL analogs have been developed for this purpose, the utility of these compounds in realizing the suicidal germination strategy for combating Striga is still largely unknown. Here, we evaluated the efficacy of three potent SL analogs (MP3, MP16, and Nijmegen-1) under laboratory, greenhouse, and farmer's field conditions. All investigated analogs showed around a 50% Striga germination rate, equivalent to a 50% reduction in infestation, which was comparable to the standard SL analog GR24. Importantly, MP16 had the maximum reduction of Striga emergence (97%) in the greenhouse experiment, while Nijmegen-1 appeared to be a promising candidate under field conditions, with a 43% and 60% reduction of Striga emergence in pearl millet and sorghum fields, respectively. These findings confirm that the selected SL analogs appear to make promising candidates as simple suicidal agents both under laboratory and real African field conditions, which may support us to improve suicidal germination technology to deplete the Striga seed bank in African agriculture.

Function of hydroxycinnamoyl spermidines in seedling growth of Arabidopsis.

Hydroxycinnamic acid amides are involved in various developmental processes as well as in biotic and abiotic stress responses. Among them, the presence of spermidine derivatives, such as N1,N8-di(coumaroyl)-spermidine and N1,N8-di(sinapoyl)-spermidine, and their biosynthetic genes have been reported in Arabidopsis, but their functions in plants are still unknown. We chemically synthesized the above-mentioned spermidine derivatives to assess their physiological functions in Arabidopsis. We evaluated the growth and development of chemically treated Arabidopsis and demonstrated that these compounds inhibited seed germination, hypocotyl elongation, and primary root growth, which could be due to modulation of plant hormone homeostasis and signaling. The results suggest that these compounds are regulatory metabolites that modulate plant growth and development.

Rational design of Striga hermonthica-specific seed germination inhibitors.

The obligate hemiparasitic weed Striga hermonthica grows on cereal roots and presents a severe threat to global food security by causing enormous yield losses, particularly in sub-Saharan Africa. The rapidly increasing Striga seed bank in infested soils provides a major obstacle in controlling this weed. Striga seeds require host-derived strigolactones (SLs) for germination, and corresponding antagonists could be used as germination inhibitors. Recently, we demonstrated that the common detergent Triton X-100 is a specific inhibitor of Striga seed germination by binding noncovalently to its receptor, S. hermonthica HYPO-SENSITIVE TO LIGHT 7 (ShHTL7), without blocking the rice (Oryza sativa) SL receptor DWARF14 (OsD14). Moreover, triazole ureas, the potent covalently binding antagonists of rice SL perception with much higher activity toward OsD14, showed inhibition of Striga but were less specific. Considering that Triton X-100 is not suitable for field application and by combining structural elements of Triton and triazole urea, we developed two hybrid compounds, KK023-N1 and KK023-N2, as potential Striga-specific germination inhibitors. Both compounds blocked the hydrolysis activity of ShHTL7 but did not affect that of OsD14. Binding of KK023-N1 diminished ShHTL7 interaction with S. hermonthica MORE AXILLARY BRANCHING 2, a major component in SL signal transduction, and increased ShHTL7 thermal specificity. Docking studies indicate that KK023-N1 binding is not covalent but is caused by hydrophobic interactions. Finally, in vitro and greenhouse tests revealed specific inhibition of Striga seed germination, which led to a 38% reduction in Striga infestation in pot experiments. These findings reveal that KK023-N1 is a potential candidate for combating Striga and a promising basis for rational design and development of further Striga-specific herbicides.

Radiosensitization using hydrogen peroxide in patients with cervical cancer.

The purpose of the present study was to analyze the feasibility and safety of radiosensitization using hydrogen peroxide for cervical cancer. In superficial tumors, breast cancer and hepatocellular carcinoma, the safety and effectiveness of radiosensitization has been reported; to the best of our knowledge, however, there are no reports on cervical cancer. A total of 20 patients with cervical cancer were recruited. Inclusion criteria were as follows: Patients who required radical external beam radiotherapy (RT); ineligible for or refused brachytherapy; age, ≥20 years; no hematogenous metastasis; Eastern Cooperative Oncology Group Performance Status up to 2; and had not undergone prior treatment. Hydrogen peroxide was used twice a week in combination with RT. A 3% hydrogen peroxide solution-soaked gauze was inserted into the vagina during RT. A total of 45 Gy was delivered in 25 fractions to the whole pelvis with a boost of 10 Gy in 5 fractions if pelvic or para-aortic metastatic lymph nodes were observed. Ultimately, 18 patients were evaluated. Among the 17 patients (excluding one patient with tumor in situ), the one- and two-year overall survival rates were both 90% in patients with stage I/II and 86% in stage III/IV cervical cancer. The adverse events were well tolerated with no severe acute or late adverse events. Although limited by small sample size, short observation time and low radiation dose, the present study demonstrated that radiosensitization treatment may be an option for patients who cannot undergo brachytherapy. The study was retrospectively registered at the university hospital medical information network center (no. UMIN000039045) on January 6, 2020.

Efficient Mimics for Elucidating Zaxinone Biology and Promoting Agricultural Applications.

Zaxinone is an apocarotenoid regulatory metabolite required for normal rice growth and development. In addition, zaxinone has a large application potential in agriculture, due to its growth-promoting activity and capability to alleviate infestation by the root parasitic plant Striga through decreasing strigolactone (SL) production. However, zaxinone is poorly accessible to the scientific community because of its laborious organic synthesis that impedes its further investigation and utilization. In this study, we developed easy-to-synthesize and highly efficient mimics of zaxinone (MiZax). We performed a structure-activity relationship study using a series of apocarotenoids distinguished from zaxinone by different structural features. Using the obtained results, we designed several phenyl-based compounds synthesized with a high-yield through a simple method. Activity tests showed that MiZax3 and MiZax5 exert zaxinone activity in rescuing root growth of a zaxinone-deficient rice mutant, promoting growth, and reducing SL content in roots and root exudates of wild-type plants. Moreover, these compounds were at least as efficient as zaxinone in suppressing transcript level of SL biosynthesis genes and in alleviating Striga infestation under greenhouse conditions, and did not negatively impact mycorrhization. Taken together, MiZax are a promising tool for elucidating zaxinone biology and investigating rice development, and suitable candidates for combating Striga and increasing crop growth.

Abdominal Myomectomy for Huge Uterine Myomas with Intra-arterial Balloon Occlusion: Approach to Reduce Blood Loss.

Abdominal myomectomy for a huge myomas, especially uterine cervical myoma, is difficult because of risks, such as intraoperative bleeding or injury to adjacent organs. Therefore, understanding of the positional relationships among a huge myoma, especially cervical or intraligamental myoma, and the vascular plexuses in the right and left cardinal ligaments is important for prevention of massive bleeding during myomectomy. While sufficiently performing preoperative assessment with pelvic examination, ultrasonography, magnetic resonance imaging (MRI), etc., surgeons should always keep in mind how they can reduce the blood loss volume, while safely and surely performing resections. For a cervical myoma of the uterus and giant uterine leiomyoma that leave no intrapelvic space and prevent palpation and identification of the uterine arteries and the internal iliac arteries, surgery can be performed safely by preoperatively placing balloon catheters in the internal iliac arteries. Hemostaic strategies for myomectomy and tips of subsequent pregnancy following myomectomy are also described.

A New Series of Carlactonoic Acid Based Strigolactone Analogs for Fundamental and Applied Research.

Strigolactones (SLs) are a group of carotenoid derived plant hormones that play a key role in establishing plant architecture and adapting it to environmental changes, and are involved in plants response to biotic and abiotic stress. SLs are also released into the soil to serve as a chemical signal attracting beneficial mycorrhizal fungi. However, this signal also induces seed germination in root parasitic weeds that represent a major global threat for agriculture. This wide spectrum of biological functions has made SL research one of the most important current topics in fundamental and applied plant science. The availability of SLs is crucial for investigating SL biology as well as for agricultural application. However, natural SLs are produced in very low amounts, and their organic synthesis is quite difficult, which creates a need for efficient and easy-to-synthesize analogs and mimics. Recently, we have generated a set of SL analogs, Methyl Phenlactonoates (MPs), which resemble the non-canonical SL carlactonoic acid. In this paper, we describe the development and characterization of a new series of easy-to-synthesize MPs. The new analogs were assessed with respect to regulation of shoot branching, impact on leaf senescence, and induction of seed germination in different root parasitic plants species. Some of the new analogs showed higher efficiency in inhibiting shoot branching as well as in triggering parasitic seed germination, compared to the commonly used GR24. MP16 was the most outstanding analog showing high activity in different SL biological functions. In summary, our new analogs series contains very promising candidates for different applications, which include the usage in studies for understanding different aspects of SL biology as well as large scale field application for combating root parasitic weeds, such as Striga hermonthica that devastates cereal yields in sub-Saharan Africa.

Methylation at the C-3' in D-Ring of Strigolactone Analogs Reduces Biological Activity in Root Parasitic Plants and Rice.

Strigolactones (SLs) regulate plant development and induce seed germination in obligate root parasitic weeds, e.g. Striga spp. Because organic synthesis of natural SLs is laborious, there is a large need for easy-to-synthesize and efficient analogs. Here, we investigated the effect of a structural modification of the D-ring, a conserved structural element in SLs. We synthesized and investigated the activity of two analogs, MP13 and MP26, which differ from previously published AR8 and AR36 only in the absence of methylation at C-3'. The de-methylated MP13 and MP26 were much more efficient in regulating plant development and inducing Striga seed germination, compared with AR8. Hydrolysis assays performed with purified Striga SL receptor and docking of AR8 and MP13 to the corresponding active site confirmed and explained the higher activity. Field trials performed in a naturally Striga-infested African farmer's field unraveled MP13 as a promising candidate for combating Striga by inducing germination in host's absence. Our findings demonstrate that methylation of the C-3' in D-ring in SL analogs has a negative impact on their activity and identify MP13 and, particularly, MP26 as potent SL analogs with simple structures, which can be employed to control Striga, a major threat to global food security.

Safety and efficacy of neoadjuvant chemotherapy with bevacizumab in advanced-stage peritoneal/ovarian cancer patients.

OBJECTIVE: The aim of this study was to evaluate the outcomes of neoadjuvant chemotherapy (NAC) with bevacizumab (Bev) at our institute. MATERIALS AND METHODS: Eleven patients with stage IIIC or IV peritoneal/ovarian cancer who underwent interval debulking surgery (IDS) after NAC with Bev between December 2014 and December 2016 were enrolled retrospectively (TCB group). As a control group, we enrolled 13 patients evaluated between December 2012 and December 2014 who underwent IDS and received NAC without Bev (TC group). Both the TCB and TC groups received combination chemotherapy consisting of paclitaxel (175 mg/m2) or docetaxel (70 mg/m2) and carboplatin (area under the curve 6 mg/mL/min) administered intravenously every 3 weeks (cycles 3-6). RESULTS: All patients in both groups underwent IDS. There were 7 (63.6%) and 8 (61.5%) cases with stage IIIC disease and 4 (36.3%) and 5 (30.7%) with stage IV disease in the TCB and TC groups, respectively. The complete resection rate was 81.8% in the TCB group and 69.2% in the TC group. The rate of achieving either complete or optimal resection was 100% in the TCB group and 69.2% in the TC group (p = 0.043). Hematoxicity (grade 3 or higher) was observed in 9 patients (81.8%) in the TCB group and 12 (92.3%) patients in the TC group. One patient (9%) in the TCB group experienced abdominal incisional hernia due to a fascial defect. CONCLUSION: IDS after NAC with Bev is safe, with a similar efficacy as that after NAC without Bev.

Drug-induced aortitis in a patient with ovarian cancer treated with bevacizumab combination therapy.

OBJECTIVE: To review and evaluate drug-induced vasculitis, which is an extremely rare complication of chemotherapy. CASE REPORT: A 47-year-old woman with ovarian cancer developed aortitis during bevacizumab combination chemotherapy. Contract-enhanced CT showed concentric thickening of the descending aorta. Antibiotics were administered, but a repeat CE-CT scan showed no resolution of the aortitis. To treat the aortitis, she was started on oral prednisolone. A subsequent CE-CT scan showed no signs of aortitis. She was thus re-started on a modified chemotherapy regimen. CONCLUSION: Aortitis should be considered in patients receiving bevacizumab combination therapy who develop persistent fever and upper-abdominal pain. Contrast-enhanced CT is useful for detecting drug-induced aortitis.

Comparison of Treatment Results for Mallet Finger Fractures in Children Between Low-Intensity Pulsed Ultrasound Stimulation and Ishiguro's Method.

BACKGROUND: We compared the treatment results for displaced mallet finger fractures in children between low-intensity pulsed ultrasound (LIPUS) stimulation and Ishiguro's method, which involves extension block and arthrodesis of the distal interphalangeal (DIP) joint with pinning. METHODS: Eleven cases (5 females and 6 males; average age, 13.5 years) of mallet finger were operated with Ishiguro's method, and 8 cases (3 females and 5 males; average age, 13.0 years) were treated with LIPUS stimulation. Lateral radiographs were used to determine the distance of fragment displacement and the percentage of the articular surface involved in the fragments. Functional outcomes in flexion and extension and those estimated using Crawford's evaluation criteria at the final visits were assessed in each group. RESULTS: The duration needed for fracture healing was longer, however, active extension and flexion of the DIP joint were significantly larger in the LIPUS group compared with those in the pinning group. Functional recovery was excellent in all cases in the LIPUS group; however, recovery was good in 3 cases and excellent in 8 cases in the pinning group. Extension of the DIP joint was significantly larger when pins were removed in 35 or lesser days postoperatively compared with cases in which pin fixation was continued for more than 35 days. CONCLUSIONS: LIPUS therapy may be recommended as an option to treat type I mallet finger in children for whom initiation of treatment was delayed up to 8 weeks. When Ishiguro's method is applied to the displaced mallet fracture in children, arthrodesis of the DIP joint for more than 5 weeks should be avoided to prevent flexion contracture.

Anti-NMDA receptor encephalitis due to large-cell neuroendocrine carcinoma of the uterus.

A 44-year-old woman presented with a large-cell neuroendocrine carcinoma and uterine endometrioid carcinoma with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis. Following the diagnosis of uterine cancer, the patient suddenly developed psychosis with abnormal behaviors, delusions, irritability, and forgetfulness. The cerebrospinal fluid tested positive for anti-NMDAR antibodies (encoding the NR1 subunit). The patient was diagnosed with paraneoplastic limbic encephalitis due to uterine cancer. Histology of multiple abdominal metastatic samples revealed a neuroendocrine tumor. Her consciousness improved temporarily after tumor resection and comprehensive immunomodulatory therapy. On day 104 after admission, the patient died of multiple organ failure. The autopsy revealed a perivascular infiltration of inflammatory cells in the amygdala and NMDAR-positive cells in the primary uterine cancer. Our findings demonstrated that neuroendocrine tumors can induce anti-NMDAR encephalitis, which is consistent with three previous reports. A comprehensive treatment with resection of the carcinoma, immunoglobulins, and plasma exchange can induce a partial improvement of the symptoms.

The efficacy and safety of combination therapy of low-intensity pulsed ultrasound stimulation in the treatment of unstable both radius and ulna fractures in children.

BACKGROUND: There are few reports of Low-intensity pulsed ultrasound (LIPUS) treatment for fresh forearm fractures in children. OBJECTIVES: LIPUS stimulation was applied after surgery of forearm fractures in children and the efficacy and safety of combination therapy of LIPUS treatment were evaluated. PATIENTS AND METHODS: Children with both radius and ulna fracture, twenty-five diaphysis (mid-R&U) and nineteen metaphysis (dist-R&U) fractures, were treated with intramedullary nailing followed by cast and splint mobilization. Thirteen patients in the mid-R&U fracture group and eight patients in the dist-R&U fracture group were combined with LIPUS stimulation postoperatively. RESULTS: Periosteal callus appeared significantly earlier after surgery in the LIPUS-treated groups than in the groups without LIPUS treatment. The duration of external fixation was significantly shorter in the dist-R&U fracture group treated with LIPUS stimulation compared with that in the mid-R&U fracture group without LIPUS treatment. Furthermore, the time span needed for bone union in the groups with LIPUS stimulation was significantly shorter than in the groups without LIPUS stimulation. CONCLUSIONS: It is suggested that LIPUS stimulation can lead to a reduction of treatment periods of unstable forearm fractures safely after operation even in children.

A phase II randomised study to evaluate the efficacy of aprepitant plus palonosetron for preventing delayed-phase CINV associated with TC therapy in gynaecological cancer.

AIM: Chemotherapy-induced nausea and vomiting (CINV) is one of the most frequently encountered side effects of cancer treatment. Severe CINV can lead patients to refuse chemotherapy, which ultimately affects cancer outcomes. The development of fairly new antiemetic agents, 5-hydroxytryptamine-3 receptor antagonists, palonosetron and neurokinin-1 receptor antagonists and aprepitant has reduced the risk and incidence of CINV. In this study, we assessed the efficacy of aprepitant plus palonosetron against palonosetron for CINV in patients receiving moderately emetic cancer chemotherapy (paclitaxel and carboplatin combination [TC] therapy). METHODS: Between November 2010 and March 2014, 78 patients with gynecological cancer treated with TC therapy were randomized into two groups: an aprepitant group (administered aprepitant, dexamethasone and palonosetron) and a control group (administered dexamethasone and palonosetron). The primary study endpoint was complete response, defined as the complete absence of emetic events in the delayed phase. RESULTS: The complete response rate in the delayed phase differed significantly between the two groups, with 82% in the aprepitant group and 97% in the control group (P = 0.025). CONCLUSION: The combination of aprepitant and palonosetron appears to be of greater efficacy than palonosetron alone for the prevention of delayed-phase CINV induced by TC therapy.