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Sucrose yield in sugarcane is a complex process regulated by both environmental and endogenous factors. However, the metabolic balance driving vegetative growth and sucrose accumulation remains poorly understood. Herein, we carried out a comprehensive assessment of carbohydrate dynamics throughout the crop cycle in two sugarcane varieties varying in biomass production, evaluating the carbon metabolism in both leaves and stalks. Our data revealed that the decline in photosynthetic rates during sugarcane maturation is associated not only to accumulation of sugars in leaves but also due to stomatal and non-stomatal limitations. We found that metabolic processes in leaves and stalks were intrinsically linked. While IACSP94-2094 had higher stalk sucrose concentration than IACSP95-5000, this latter produced more biomass. Compared to IACSP95-5000, IACSP94-2094 showed higher sucrose phosphate synthase (SPS) activity in leaves and stalks, along with lower soluble acid invertase (SAI) activity in leaves during the maximum growth stage. Interestingly, IACSP94-2094 also exhibited higher stalk SPS activity and lower stalk SAI activity than IACSP95-5000 during maturation. High biomass production by IACSP95-5000 was associated with higher sucrose synthase (SuSy) and SAI activity in leaves and higher SuSy and soluble neutral invertase (SNI) activity in stalks when compared to IACSP94-2094 during the maximum growth. Despite the contrasting strategies, both varieties displayed similar total sucrose yield, a balance between sucrose concentration and biomass production. This phenomenon implies the presence of a compensatory mechanism in sugarcane, with high biomass production compensating low sucrose accumulation and vice versa.
The intentional use of drugs before or during sexual intercourse (chemsex) is a phenomenon of special importance in the MSM (men who have sex with men) population due to its impact on mental, physical and sexual health. Sexual health issues related to chemsex practice have been described such as difficulties in achieving sober sex, erectile dysfunction or problems with sexual desire.
Objectives
The objective of this study was to understand the impact of chemsex on sexual health and sexual response by the participantes of a sexual health program for chemsex users in two Substance Use Disorder Clinics in Madrid.
Methods
Qualitative research approach. We analyze an anonymous survey with chemsex users with open answer questions about the impact of chemsex practice on sexual response and sexual health. Data analysis was based on thematic analysis of content.
Results
Several differences were identifed between chemsex and sober sex. In sober sex it can take longer to feel aroused, sexual desire is more context-dependent and more easyly controled. They connect easily with other people needs when they had sober sex. They described difficulties with consent with some sexual practices when they were on drugs. Shame and guilt was associated with chemsex. They describe more arousal, more independent of the erotic context, longer sexual intercourse and delayed ejaculation when they had sex under the influence of drugs.
Conclusions
Chemsex is a phenomenon that needs a multidisciplinary approach and mental and sexual health must be taken into account including sexological perspective. Interventions that provide sexual counselling and sexual therapy for chemsex users must be developped.
The intentional use of drugs before or during sexual intercourse (chemsex) is a phenomenon of special importance in the MSM (men who have sex with men) population due to its impact on mental, physical and sexual health. Sexual health issues related to chemsex practice have been described such as difficulties in achieving sober sex, erectile dysfunction or problems with sexual desire.Objectives: The objective of this study was to understand the sexual motivations for chemsex practice o a group participantes of a sexual health program for chemsex users in two Drug Substace Use Disorder Clinics in Madrid.
Methods
Qualitative research approach. We analyze an anonymous survey with chemsex users with open answer questions about the motivations for chemsex practice. Data analysis was based on thematic analysis of content.
Results
Different qualitative studies have examined the motivations for engaging in chemsex. The participants identified two main raisons: pleasure and losing inhibitions. We analyed the inhibitions described by participants: difficulties with arousal, ejaculation, social interaction in sexual context, difficulties in situations that require intimacy, sexual practices that make them feel guilt/shame (for example BDSM) problems with “erotic” self-esteem: rejection of non-normative bodies or towards non- normative gender expression perceived as undesirable.
Conclusions
Understanding the sexual motivations for engaging in chemsex seems necessary to develop and multidisciplinary approach. Mental health proffesionals should consider sexual counselling and sexual therapy for chemsex users in their treatment.
Metabolic dysfunction and excess accumulation of adipose tissue are detrimental side effects from breast cancer treatment. Diet and physical activity are important treatments for metabolic abnormalities, yet patient compliance can be challenging during chemotherapy treatment. Time-restricted eating (TRE) is a feasible dietary pattern where eating is restricted to 8 h/d with water-only fasting for the remaining 16 h. The purpose of this study is to evaluate the effect of a multimodal intervention consisting of TRE, healthy eating, and reduced sedentary time during chemotherapy treatment for early-stage (I–III) breast cancer on accumulation of visceral fat (primary outcome), other fat deposition locations, metabolic syndrome and cardiovascular disease risk (secondary outcomes) compared with usual care. The study will be a two-site, two-arm, parallel-group superiority randomised control trial enrolling 130 women scheduled for chemotherapy for early-stage breast cancer. The intervention will be delivered by telephone, including 30–60-minute calls with a registered dietitian who will provide instructions on TRE, education and counselling on healthy eating, and goal setting for reducing sedentary time. The comparison group will receive usual cancer and supportive care including a single group-based nutrition class and healthy eating and physical activity guidelines. MRI, blood draws and assessment of blood pressure will be performed at baseline, after chemotherapy (primary end point), and 2-year follow-up. If our intervention is successful in attenuating the effect of chemotherapy on visceral fat accumulation and cardiometabolic dysfunction, it has the potential to reduce risk of cardiometabolic disease and related mortality among breast cancer survivors.
We sought to determine whether an electronic hand hygiene (HH) system could monitor HH compliance at similar rates to direct human observation.
Methods:
This 4-year proof-of-concept study was conducted in an intensive care unit (ICU) of a private tertiary-care hospital in São Paulo, Brazil, where electronic HH systems were installed in 2 rooms. HH compliance was reported respectively using direct observation and electronic counter devices with an infrared system for detecting HH opportunities.
Results:
In phase 1, HH compliance by human observers was 56.3% (564 of 1,001 opportunities), while HH compliance detected by the electronic observer was 51.0% (515 of 1,010 opportunities). In phase 2, human observers registered 484 HH opportunities with a HH compliance rate of 64.7% (313 of 484) versus 70.6% (346 of 490) simultaneously detected by the electronic system. In addition, an enhanced HH electronic system monitored activity 24 hours per day and HH compliance without the presence of a human observer was 40.3% (10,642 of 26,421 opportunities), providing evidence for the Hawthorne effect.
Conclusions:
The electronic HH monitoring system had good correlation with human HH observation, but compliance was remarkably lower when human observers were not present due to the Hawthorne effect (25%–30% absolute difference). Electronic monitoring systems can replace direct observation and can markedly reduce the Hawthorne effect.
Most hand hygiene (HH) intervention studies use a quasi-experimental design, are primarily uncontrolled before-and-after studies, or are controlled before-and-after studies with a nonequivalent control group. Well-funded studies with improved designs and HH interventions are needed.
Objectives:
To evaluate healthcare worker (HCW) HH compliance with alcohol-based hand rub (ABHR) through direct observation (human observer), 2 electronic technologies, a radio frequency identification (RFID) badge system, and an invasive device sensor.
Methods:
In our controlled experimental study, 2,269 observations were made over a 6-month period from July 1 to December 30, 2020, in a 4-bed intensive care unit. We compared HH compliance between a basic feedback loop system with RFID badges and an enhanced feedback loop system that utilized sensors on invasive devices.
Results:
Real-time feedback by wireless technology connected to a patient’s invasive device (enhanced feedback loop) resulted in a significant increase in HH compliance (69.5% in the enhanced group vs 59.1% in the basic group; P = .0001).
Conclusion:
An enhanced feedback loop system connected to invasive devices, providing real-time alerts to HCWs, is effective in improving HH compliance.
There is a growing interest in the emotional state of cancer patients. The main objective of this pilot study is to assess the feasibility, acceptability, and preliminary efficacy of Meaning-Centered Psychotherapy and Essential Care (MCP-EC) in patients with advanced cancer compared with usual psychological support. We define “Essential Care” as the promotion of patient care and self-care through the recall of good care experiences and discussion of the concepts: responsibility, self-compassion, kindness, and attitude.
Method
Pilot, single-center, and prospective study of 30 patients with advanced cancer and emotional distress. Our adaptation consisted in three session Meaning-Centered Psychotherapy-Palliative Care, plus a fourth session named “Essential Care”. The study was carried out in two phases. First, 20 patients were randomized to one of the two arms: individual MCP-EC (experimental, n = 10) or usual psychological supportive (control, n = 10). In a second phase, 10 patients were assigned consecutively to Group MCP-EC (n = 10). All patients were evaluated at baseline (pre-) and post-intervention with questionnaires for sociodemographic data and clinical scales.
Results
Nineteen patients completed the 4 sessions of MCP-EC, 9 individual format and 10 group format. Usual supportive intervention was delivered to 10 control patients. Total 28 patients completed pre- and post-treatment evaluations. There were no pre- vs. post-differences in the evaluations of the control group. In the experimental group, significant pre- vs. post-differences were found in EQ-5D-3L, HADS, FACIT, DM, HAI, SCS-SF, and TD questionnaires. These results indicated that MCP-EC reduced anxiety and depression symptoms, hopelessness, demoralization, as well as increased spiritual well-being and sense of meaning. Participants were satisfied and found the MCP-EC intervention positively.
Conclusions
This pilot study suggests that the MCP-EC has feasibility, acceptability, and preliminary efficacy reducing the emotional distress in advanced cancer patients. Larger studies are warranted to clarify the strengths and limitations of this psychotherapy.
The global coronavirus disease 2019 (COVID-19) pandemic has altered entire nations and their health systems. The greatest impact of the pandemic has been seen among vulnerable populations, such as those with comorbidities like heart diseases, kidney failure, obesity, or those with worse health determinants such as unemployment and poverty. In the current study, we are proposing previous exposure to fine-grained volcanic ashes as a risk factor for developing COVID-19. Based on several previous studies it has been known since the mid 1980s of the past century that volcanic ash is most likely an accelerating factor to suffer from different types of cancer, including lung or thyroid cancer. Our study postulates, that people who are most likely to be infected during a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) widespread wave will be those with comorbidities that are related to previous exposure to volcanic ashes. We have explored 8703 satellite images from the past 21 y of available data from the National Oceanic and Atmospheric Administration (NOAA) database and correlated them with the data from the national institute of health statistics in Ecuador. Additionally, we provide more realistic numbers of fatalities due to the virus based on excess mortality data of 2020-2021, when compared with previous years. This study would be a very first of its kind combining social and spatial distribution of COVID-19 infections and volcanic ash distribution. The results and implications of our study will also help countries to identify such aforementioned vulnerable parts of the society, if the given geodynamic and volcanic settings are similar.
Adoption, twin and family studies suggest that suicide behavior is familial and heritable. Both completed and attempted suicide appear to be transmitted in a familial form. Genetics and environment influences had been detected in various studies. But suicidal behavior suggests to be inherited independently from the mental disorders usually associated with it. While traditional statistics emphasizes inference and estimations, data mining emphasizes the fulfillment of a task such as classification, estimation, or knowledge discovery.
Objectives:
The goal of this study was to determine in a large sample of suicide attempts which variables are associated with family history of attempted suicide.
Methods:
In an emergency room, 539 adult suicide attempters were recruited. The two dichotomous dependent variables were family history of suicide attempt (10%) and of completed suicide (4%). Independent variables were 101 clinical variables explored with two data mining techniques: Random Forest and Forward Selection.
Results:
A model for family history of completed suicide could not be developed. A classificatory model for family history of attempted suicide included the use of alcohol in the intent and family history of completed suicide, provide a sensitivity of 78.4%, a specificity of 98.7% and accuracy of 96.6%.
Conclusions:
A classificatory model for family history of completed suicide could not be developed using data mining techniques. But it suggested that the use of alcohol in the intent and family history of completed suicide may be associated with familial attempted suicide.
Mycotoxins are present in almost all feedstuffs used in animal nutrition but are often ignored in beef cattle systems, even though they can affect animal performance. The objective of this study was to evaluate the effects of mycotoxins and a mycotoxin adsorbent (ADS) on performance of Nellore cattle finished in a feedlot. One hundred Nellore cattle (430 ± 13 kg) were used in a randomized complete block design with a 2 × 2 factorial arrangement of treatments. The factors consisted of two diets with either natural contamination (NC) or exogenous contamination (EC) and the presence (1 g/kg of DM; ADS) or absence of a mycotoxin adsorbent. The NC and EC diets had the following contaminations, respectively: 0.00 and 10.0 µg/kg aflatoxins, 5114 and 5754 µg/kg fumonisins, 0.00 and 42.1 µg/kg trichothecenes B, 0.00 and 22.1 µg/kg trichothecenes A and 42.9 and 42.9 µg/kg fusaric acid. At the beginning of the experiment, all animals were weighed, and four randomly selected animals were slaughtered to evaluate the initial carcass weight. After 97 days of treatment, all animals were weighed and slaughtered. There was no interaction among factors for the DM intake (DMI; P = 0.92); however, there was a tendency for the EC diets to decrease the DMI by 650 g/day compared to animals fed NC diets (P = 0.09). There was a trend for interaction among factors (P = 0.08) for the average daily gain (ADG), where the greatest ADG was observed for cattle fed the NC diet (1.77 kg), and the lowest was observed for those fed the EC diet (1.51 kg). The NC + ADS and EC + ADS treatments presented intermediate values for ADG. The animals fed the NC diet had a greater final BW (596 kg) than animals fed the EC treatment (582 kg; P = 0.04). There was a tendency for interaction among factors for carcass gain (P = 0.08). Similarly to ADG, the highest carcass gain was observed for animals fed the NC diet (1.20 kg), and the lowest was observed for those fed the EC diet (1.05 kg). The NC + ADS and EC + ADS treatments presented intermediate values. The natural contamination groups had greater carcass gain than that of the EC groups, and the use of the ADS recovered part of the weight gain in animals fed the EC diet. In conclusion, mycotoxins at the levels evaluated affected the performance of beef cattle, and adsorbents may mitigate their impact.
The start of Child and Adolescent attention to gender dysphoria is very recent. In our Unit, it has objectified a growing increase in such demand over recent years.
As a typical example would be a patient of 13 years following gender dysphoria begins to present school failure and behavior problems at home with emotional instability.
According to the recommendations of the Group Identity and Sexual Differentiation (GIDSEEN) after early detection is to guide parents towards a comprehensive treatment at a specialized interdisciplinary teams and a psychosocial approach to improve the quality of life, decrease mental comorbidity and gender dysphoria own. Having no such care in our community has been necessary to make a referral to another community to attend this demand.
Currently it is giving adequate attention to these cases, but except for referral to another community. However, as we are seeing progression care in our area in the future could be feasible. Therefore, we consider as a first step dysphoria quantify each case in our area.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Early life adversity plays a critical role in the emergence of borderline personality disorder (BPD) and this could occur through epigenetic programming. In this perspective, we aimed to determine whether childhood maltreatment could durably modify epigenetic processes by the means of a whole-genome methylation scan of BPD subjects. Using the Illumina Infinium® Human Methylation450 BeadChip, global methylation status of DNA extracted from peripheral blood leucocytes was correlated to the severity of childhood maltreatment in 96 BPD subjects suffering from a high level of child adversity and 93 subjects suffering from major depressive disorder (MDD) and reporting a low rate of child maltreatment. Several CpGs within or near the following genes (IL17RA, miR124-3, KCNQ2, EFNB1, OCA2, MFAP2, RPH3AL, WDR60, CST9L, EP400, A2ML1, NT5DC2, FAM163A and SPSB2) were found to be differently methylated, either in BPD compared with MDD or in relation to the severity of childhood maltreatment. A highly relevant biological result was observed for cg04927004 close to miR124-3 that was significantly associated with BPD and severity of childhood maltreatment. miR124-3 codes for a microRNA (miRNA) targeting several genes previously found to be associated with BPD such as NR3C1. Our results highlight the potentially important role played by miRNAs in the etiology of neuropsychiatric disorders such as BPD and the usefulness of using methylome-wide association studies to uncover such candidate genes. Moreover, they offer new understanding of the impact of maltreatments on biological processes leading to diseases and may ultimately result in the identification of relevant biomarkers.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
This is a case report of a 63-year-old patient with no previous attentions in mental health. He is referred by his general practitioner because he presents wounds all over his body. He reports that there is a plague of bugs at his place that bite him everywhere. Therefore, he scratches continuously, trying to remove the stingers, and injuring himself all over. The family ensures there are no bugs at all, but the patient threatens to set fire to the house in order to extinguish the plague or even kill himself. An OCD with cleaning compulsive behavior was also present since many years, as well as an alcohol abuse. The patient required hospitalization in the psychiatry service. Organic cause for the disorder was discarded. Long-acting injectable aripiprazol was introduced and the patient stopped drinking. Progressively, the delusional symptoms began to subside. Now he maintains no awareness of illness but he says the bugs are disappearing and, at least, they do not bite him anymore.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Maintaining antipsychotic therapy in mental disorder is important in preventing relapse, rehospitalization, and suicide. Lack of awareness of illness may be a leading cause for non-adherence. Long-acting depot can prevent non- adherence and thus potentially contribute to better patient outcomes.
Objective
The aim of this prospective, observational, non interventional 2-year-long study is to assess severity and post-intervention changes and attitudes toward medication of a group of patients treated paliperidone palmitate (PP).
Methods
Thirty-three outpatients stabilised with PP during the last 24 months. Inclusion criteria were: patients’ age (> 18 years), a diagnosis of schizophrenia, bipolar disorder, schizoaffective disorder stabilised during the last 12 months with PP, without a diagnostics from axis I or II (except for nicotine of caffeine) and able to sign the inform consent. Data collected: general sociodemographic and clinical data (age, sex, level of education, socioeconomic situation, family support, psychiatric diagnosis, years of evolution, use/abuse of substances, treatment, previous and later number of hospitalisations. Evaluations included disease severity (Clinical Global Impression-Severity (CGI-S) and Drug Attitude Inventory, (DAI)).
Results
Thirty-threeoutpatients were followed during 24 months [mean dose 132,58 (44,4) mg], 75,8% were men, age 45,05 years old, 87,8% with a diagnoses of paranoid schizophrenia. Antipsychotic monotherapy increased over the time with PP. Significant improvements were observed on both Clinical Global Impression and Drug Attitude Inventory. The number of rehospitalizations and mean stays decreased from the beginning until the end of these 24 months.
Conclusions
Our results suggest an improvement in the patient's clinical vision and attitude towards medication with long-acting depot.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Early life adversity plays a critical role in the emergence of borderline personality disorder (BPD) and this could occur through epigenetic programming. In this perspective, we aimed to determine whether childhood maltreatment could durably modify epigenetic processes by the means of a whole-genome methylation scan of BPD subjects. Using the Illumina Infinium® Human Methylation 450 Bead Chip, global methylation status of DNA extracted from peripheral blood leucocytes was correlated to the severity of childhood maltreatment in 96 BPD subjects suffering from a high level of child adversity and 93 subjects suffering from major depressive disorder (MDD) and reporting a low rate of child maltreatment. Several CpGs within or near the following genes (IL17RA, miR124-3, KCNQ2, EFNB1, OCA2, MFAP2, RPH3AL, WDR60, CST9L, EP400, A2ML1, NT5DC2, FAM163A and SPSB2) were found to be differently methylated, either in BPD compared with MDD or in relation to the severity of childhood maltreatment. A highly relevant biological result was observed for cg04927004 close to miR124-3 that was significantly associated with BPD and severity of childhood maltreatment. miR124-3 codes for a microRNA (miRNA) targeting several genes previously found to be associated with BPD such as NR3C1. Our results highlight the potentially important role played by miRNAs in the etiology of neuropsychiatric disorders such as BPD and the usefulness of using methylome-wide association studies to uncover such candidate genes. Moreover, they offer new understanding of the impact of maltreatments on biological processes leading to diseases and may ultimately result in the identification of relevant biomarkers.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Evidence on whether nutritional supplementation affects physical activity (PA) during early childhood is limited. We examined the long-term effects of lipid-based nutrient supplements (LNS) on total PA, moderate-to-vigorous PA (MVPA) and sedentary behaviour (SB) of children at 4–6 years using an accelerometer for 1 week. Their mothers were enrolled in the International Lipid-based Nutrient Supplement-DYAD randomised controlled trial in Ghana, assigned to daily LNS or multiple micronutrients (MMN) during pregnancy through 6 months postpartum or Fe and folic acid (IFA) during pregnancy and placebo for 6 months postpartum. From 6 to 18 months, children in the LNS group received LNS; the other two groups received no supplements. Analysis was done with intention to treat comparing two groups: LNS v. non-LNS (MMN+ IFA). Of the sub-sample of 375 children fitted with accelerometers, 353 provided sufficient data. Median vector magnitude (VM) count was 1374 (interquartile range (IQR) 309), and percentages of time in MVPA and SB were 4·8 (IQR 2) and 31 (IQR 8) %, respectively. The LNS group (n 129) had lower VM (difference in mean −73 (95 % CI −20, −126), P = 0·007) and spent more time in SB (LNS v. non-LNS: 32·3 v. 30·5 %, P = 0·020) than the non-LNS group (n 224) but did not differ in MVPA (4·4 v. 4·7 %, P = 0·198). Contrary to expectations, provision of LNS in early life slightly reduced the total PA and increased the time in SB but did not affect time in MVPA. Given reduced social-emotional difficulties in the LNS group previously reported, including hyperactivity, one possible explanation is less restless movement in the LNS group.
The aim of this study was to characterise changes in lean soft tissue (LST) and examine the contributions of energy intake, physical activity and breast-feeding practices to LST changes at 3 and 9 months postpartum. We examined current weight, LST (via dual-energy X-ray absorptiometry), dietary intake (3-d food diary), physical activity (Baecke questionnaire) and breast-feeding practices (3-d breast-feeding diary) in forty-nine women aged 32·9 (sd 3·8) years. Changes in LST varied from −2·51 to +2·50 kg with twenty-nine women gaining LST (1·1 (sd 0·7) kg, P<0·001) and twenty women losing LST (−0·9 (sd 0·8) kg, P<0·001). Energy intake (133 (SD 42) v. 109 (SD 33) kJ/kg, P=0·019) and % kJ from fat at 3 months postpartum was higher in women who gained LST at 9 months postpartum (gained LST=34 (sd 5) % kJ; lost LST=29 (sd 4) % kJ, P=0·002). Women who gained LST reported breast-feeding their infants more frequently (gained LST=8 (sd 3) feeds/d; lost LST=5 (sd 1) feeds/d, P=0·014) and for more time per d (gained LST=115 (sd 78) min/d; lost LST=59 (sd 34) min/d, P=0·016) at 9 months postpartum. Energy intake and % kJ from fat at 3 months were significant predictors of LST gain (β=0·08 (se 0·04) and 0·24 (se 0·09), respectively). This suggests that gain in LST may be associated with more frequent and longer episodes of breast-feeding at 9 months postpartum as well as dietary intake early in the postpartum period.
Current standard-of-care for glioblastoma (GBM) includes surgery, radiation and temozolomide. Most tumors recur within a year from diagnosis and median survival for recurrent GBM (rGBM) is 3-9 months. Unmethylated promoter status for O6-methylguanine-DNA-methyltransferase (MGMT) is a validated biomarker for temozolomide-resistance, exhibited by most GBM patients. VAL-083 is a DNA-targeting agent with a mechanism-of-action that is independent of MGMT. VAL-083 overcomes temozolomide-resistance in GBM cell-lines, cancer stem cells, and in vivo models. VAL-083 readily crosses the blood-brain barrier and accumulates in brain-tumor tissue. We recently completed a VAL-083 dose-escalation trial in temozolomide- and bevacizumab-refractory rGBM and determined that 40mg/m2/day given intravenously on days 1,2,3 of a 21-day cycle is generally well-tolerated. This dosing regimen was selected for subsequent GBM trials, including an ongoing single-arm, biomarker-driven Phase 2 trial (N=48) in temolozomide-refractory, bevacizumab-naïve rGBM , MGMT-unmethylated (Clinicaltrials.gov:NCT02717962). The primary objective of this study is to determine if VAL-083 improves OS compared to a historical control of 7.15 months for MGMT-unmethylated rGBM patients treated with lomustine (EORTC26101). In addition, another single-arm, biomarker-driven, Phase 2 study (N=25) of VAL-083 in combination with radiotherapy in newly diagnosed GBM, MGMT-unmethylated is ongoing (Clinicaltrials.gov:NCT03050736). This trial aims to determine a dose for further study of VAL-083 in combination with radiotherapy and explore if VAL-083 improves PFS and OS compared to historical results in newly diagnosed GBM. Enrollment and safety data updates will be provided at the meeting. The results of these studies, if successful, may support VAL-083 as part of a new chemotherapeutic treatment paradigm for GBM.
Wild mustard (Sinapis arvensis L.) is a weed that frequently infests winter wheat (Triticum aestivum L.) fields in Golestan province, Iran. Tribenuron-methyl (TM) has been used recurrently to control this species, thus selecting for resistant S. arvensis populations. The objectives were: (1) to determine the resistance level to TM of 14 putatively resistant (PR) S. arvensis populations, collected from winter wheat fields in Golestan province, Iran, in comparison to one susceptible (S) population; and (2) to characterize the resistance mechanisms and the potential evolution of cross-resistance to other classes of acetolactate synthase (ALS)-inhibiting herbicides in three populations (AL-3, G-5, and Ag-Sr) confirmed as being resistant (R) to TM. The TM doses required to reduce the dry weight of the PR populations by 50% were between 2.2 and 16.8 times higher than those needed for S plants. The ALS enzyme activity assays revealed that the AL-3, G-5, and Ag-Sr populations evolved cross-resistance to the candidate ALS-inhibiting herbicides from the sulfonylureas (SU), triazolopyrimidines (TP), pyrimidinyl-thiobenzoates (PTB), sulfonyl-aminocarbonyl-triazolinone (SCT), and imidazolinones (IMI) classes. No differences in absorption, translocation, or metabolism of [14C]TM between R and S plants were observed, suggesting that these non-target mechanisms were not responsible for the resistance. The ALS gene of the R populations contained the Trp-574-Leu mutation, conferring cross-resistance to the SU, SCT, PTB, TP, and IMI classes. The Trp-574-Leu mutation in the ALS gene conferred cross-resistance to ALS-inhibiting herbicides in S. arvensis from winter wheat fields in Golestan province. This is the first TM resistance case confirmed in this species in Iran.