Allogeneic transplant with reduced intensity conditioning regimens may overcome the poor prognosis of B-cell chronic lymphocytic leukemia with unmutated immunoglobulin variable heavy-chain gene and chromosomal abnormalities (11q- and 17p-).

PURPOSE: To evaluate the efficacy of reduced intensity conditioning (RIC) allogeneic transplant in 30 patients with poor-prognosis chronic lymphocytic leukemia (CLL) and/or high-risk molecular/cytogenetic characteristics. EXPERIMENTAL DESIGN: Eighty-three percent of patients had active disease at the moment of transplant. That is, 14 of the 23 patients analyzed (60%) had unmutated immunoglobulin variable heavy-chain gene (IgV(H)) status; 8 of 25 patients (32%) had 11q-, with four of them also displaying unmutated IgV(H); and six (24%) had 17p- (five were also unmutated). RESULTS: After a median follow-up of 47.3 months, all 22 patients alive are disease free; overall survival and event-free survival (EFS) at 6 years were 70% and 72%, respectively. According to molecular/cytogenetic characteristics, overall survival and EFS for unmutated CLL and/or with 11q- aberration (n = 13) were 90% and 92%, respectively, not significantly different to those with normal in situ hybridization, 13q- and +12, or mutated CLL (n = 7). All six patients with 17p deletion were transplanted with active disease, including three with refractory disease; all except one reached complete remission after the transplant and two are alive and disease free. Nonrelapse mortality (NRM) was 20%; more than two lines before transplant is an independent prognostic factor for NRM (P = 0,02), EFS (P = 0.02), and overall survival (P = 0.01). Patients older than 55 years have a higher risk of NRM (hazard ratio, 12.8; 95% confidence interval, 1.5-111). Minimal residual disease was monitored by multiparametric flow cytometry in 21 patients. Clearance of CD79/CD5/CD19/CD23 cells in bone marrow was achieved in 68% and 94% of the patients at days 100 and 360, respectively. CONCLUSION: According to these results, RIC allogeneic transplant could overcome the adverse prognosis of patients with unmutated CLL as well as those with 11q- or 17p-.     

Economic choice between remifentanil and food in squirrel monkeys

Traditional approaches for evaluating if compounds are reinforcing, and thus a risk for abuse, include preclinical self-administration procedures conducted in the absence of alternative reinforcers. While the track record of this approach for determining abuse potential is good, that for predicting efficacy of addiction treatments is not. An alternate approach would be economic choice between drug and nondrug rewards, with parametrically varied options from trial to trial. This would promote goal-directed decisions between reward modalities and should provide metrics that reflect changes in internal state that influence desirability of a given option. We report herein a high throughput economic choice procedure in which squirrel monkeys choose between a short-lived opiate, remifentanil, and a palatable food reward. Stimuli on touchscreens indicate the amount of each reward type offered by varying the number of reward-specific elements. The rapid clearance of remifentanil avoids accumulation of confounding levels of drug, and permits a large number of trials with a wide range of offers of each reward modality. The use of a single metric encompassing multiple values of each reward type within a session enables estimation of indifference values using logistic regression. This indifference value is sensitive to reward devaluation within each reward domain, and is therefore a useful metric for determining shifts in reward preference, as shown with satiation and pharmacological treatment approaches.Subject terms: Addiction, Decision     

Diet Modification before or during Pregnancy on Maternal and Foetal Outcomes in Rodent Models of Maternal Obesity

The obesity epidemic has serious implications for women of reproductive age; its rising incidence is associated not just with health implications for the mother but also has transgenerational ramifications for the offspring. Increased incidence of diabetes, cardiovascular disease, obesity, and kidney disease are seen in both the mothers and the offspring. Animal models, such as rodent studies, are fundamental to studying maternal obesity and its impact on maternal and offspring health, as human studies lack rigorous controlled experimental design. Furthermore, the short and prolific reproductive potential of rodents enables examination across multiple generations and facilitates the exploration of interventional strategies to mitigate the impact of maternal obesity, both before and during pregnancy. Given that obesity is a major public health concern, it is important to obtain a greater understanding of its pathophysiology and interaction with reproductive health, placental physiology, and foetal development. This narrative review focuses on the known effects of maternal obesity on the mother and the offspring, and the benefits of interventional strategies, including dietary intervention, before or during pregnancy on maternal and foetal outcomes. It further examines the contribution of rodent models of maternal obesity to elucidating pathophysiological pathways of disease development, as well as methods to reduce the impact of obesity on the mothers and the developing foetus. The translation of these findings into the human experience will also be discussed.     

Effects of Osseodensification on Immediate Implant Placement: Retrospective Analysis of 211 Implants

Osseodensification is a new method of bone instrumentation for dental implant placement that preserves bulk bone and increases primary implant stability, and may accelerate the implant rehabilitation treatment period and provide higher success and survival rates than conventional methods. The aim of this retrospective study was to evaluate and discuss results obtained on immediate implant placement with immediate and delayed loading protocols under Osseodensification bone instrumentation. This study included private practice patients that required dental implant rehabilitation, between February 2017 and October 2019. All implants were placed under Osseodensification and had to be in function for at least 12 months to be included on the study. A total of 211 implants were included in the study, with a 98.1% total survival rate (97.9% in the maxilla and 98.5% in the mandible). For immediate implants with immediate load, 99.2% survival rate was achieved, and 100% survival rate for immediate implant placement without immediate load cases. A total of four implants were lost during this period, and all of them were lost within two months after placement. Within the limitations of this study, it can be concluded that Osseodensification bone instrumentation provided similar or better results on survival rates than conventional bone instrumentation.     

Liquid profiling of circulating tumor DNA in colorectal cancer: steps needed to achieve its full clinical value as standard care

The analysis of circulating tumor DNA (ctDNA) is at the threshold of implementation into standard care for colorectal cancer (CRC) patients. However, data about the clinical utility of liquid profiling (LP), its acceptance by clinicians, and its integration into clinical workflows in real‐world settings remain limited. Here, LP tests requested as part of routine care since 2016 were retrospectively evaluated. Results show restrained request behavior that improved moderately over time, as well as reliable diagnostic performance comparable to translational studies, with an overall agreement of 91.7%. Extremely low ctDNA levels at < 0.1% in over 20% of cases, a high frequency of concomitant driver mutations (in up to 14% of cases), and ctDNA levels reflecting the clinical course of disease were revealed. However, certain limitations hampering successful translation of ctDNA into clinical practice were uncovered, including the lack of clinically relevant ctDNA thresholds, appropriate time points of LP requests, and integrative evaluation of ctDNA, imaging, and clinical findings. In conclusion, these results highlight the potential clinical value of LP for CRC patient management and demonstrate issues that need to be addressed for successful long‐term implementation in clinical workflows.     

Effects of Sand-Based Plyometric-Jump Training in Combination with Endurance Running on Outdoor or Treadmill Surface on Physical Fitness in Young Adult Males

This study aimed at examining the effects of nine weeks of sand-based plyometric-jump training (PJT) combined with endurance running on either outdoor or treadmill surface on measures of physical fitness. Male participants (age, 20.1 ± 1.7 years) were randomly assigned to a sand-based PJT combined with endurance running on outdoor surface (OT, n = 25) or treadmill surface (TT, n = 25). The endurance running intervention comprised a mixed training method, i.e., long slow distance, tempo, and interval running drills. A control group was additionally included in this study (CG, n = 25). Participants in CG followed their regular physical activity as OT and TT but did not receive any specific intervention. Individuals were assessed for their 50-m linear sprint time, standing long jump (SLJ) distance, cardiorespiratory fitness (i.e., Cooper test), forced vital capacity (FVC), calf girth, and resting heart rate (RHR). A three (groups: OT, TT, CG) by two (time: pre, post) ANOVA for repeated measures was used to analyze the exercise-specific effects. In case of significant group-by-time interactions, Bonferroni adjusted paired (within-group) and independent (between-group comparisons at post) t-tests were used for post-hoc analyses. Significant group-by-time interactions were found for all dependent variables (p < 0.001 – 0.002, ɳ_p² = 0.16 – 0.78). Group-specific post-hoc tests showed improvements for all variables after OT (p < 0.001, Hedges’g effect size [g] = 0.05 – 1.94) and TT (p < 0.001, g = 0.04 – 2.73), but not in the CG (p = 0.058 – 1.000, g = 0.00 – 0.34). Compared to CG, OT showed larger SLJ (p = 0.001), cardiorespiratory fitness (p = 0.004), FVC (p = 0.008), and RHR (p < 0.001) improvements. TT showed larger improvements in SLJ (p = 0.036), cardiorespiratory fitness (p < 0.001), and RHR (p < 0.001) compared with CG. Compared to OT, TT showed larger improvements for SLJ (p = 0.018). In conclusion, sand-based PJT combined with either OT or TT similarly improved most measures of physical fitness, with greater SLJ improvement after TT. Coaches may use both concurrent exercise regimes based on preferences and logistical constrains (e.g., weather; access to treadmill equipment). Key points

• Concurrent training in the form of sand-based plyometric-jump training and endurance running exercise can enhance physical fitness in young individuals;
• Compared to treadmill running, rating of perceived exertion was higher in outdoor running sessions;
• Sand-based plyometric-jump training may induce greater standing long jump performance when combined with endurance running on treadmill surface as compared to outdoor surface.

Key words: Muscle strength, musculoskeletal and neural physiological phenomena, movement, resistance training, high-intensity interval training, exercise     

Use of ginger to control nausea and vomiting caused by chemotherapy in patients with cervical cancer undergoing treatment: An experiment

Introduction:Uterine cervix tumors have an invasive nature, with the capacity to proliferate to surrounding organs such as the vagina, bladder, and rectum, as well as the capacity for dissemination and involvement of structures distant from its place of origin. According to the International Federation of Gynecology and Obstetrics, patients with stages IB I, IB I microscopic (small dimension <4 cm) are indicated for radiotherapy or adjuvant chemoradiotherapy with cisplatin (40 mg/m²). However, cisplatin has side effects such as hematological implications (anemia, neutropenia, and thrombocytopenia), gastrointestinal disorders (nausea, vomiting, diarrhea, constipation), and fatigue. Zingiber officinale contains bioactive compounds that act on pregnancy and postoperative nausea, chemotherapy-induced nausea and vomiting, and also in the management of fatigue, myalgia, and insomnia. This study aimed to evaluate the effects of ginger on chemotherapy-induced nausea and vomiting in patients with cervical cancer undergoing treatment with cisplatin and radiotherapy.Methods and analyses:A randomized intervention clinical and controlled trial with a triple-blind design is described, comparing the effects of institutional antiemetic therapy alone, as well as in combination with 2 different ginger concentrations.Ethics and dissemination:Due to the nature of the study, we obtained approval from the Division Ethics Committee of Liga Contra o Câncer. All participants signed an informed consent form prior to randomization. The results of this study will be published in peer-reviewed journals. The data collected will also be available in a public repository of data.Trial registration number:This study is registered in the Brazilian Registry of Clinical Trials under number RBR-47yx6p9. This study was approved by the Division Ethics Committee of Liga Contra o Câncer under CAAE 40602320.0.0000.5293.     

Gastroprotective effect of a flavone from Lonchocarpus araripensis Benth. (Leguminosae) and the possible mechanism

The gastroprotective effect of DDF (3,6-dimethoxy-6', 6'-dimethyl-[2', 3' : 7,8]-chromeneflavone) from Lonchocarpus araripensis Benth. (Leguminosae) on gastric damage induced by absolute ethanol (96%, 0.2 mL/mouse) and indometacin (30 mg kg(-1), p.o.) in mice was investigated. Intraperitoneally administered DDF at dose levels of 50, 100 and 200 mg kg(-1) markedly reduced the gastric lesions in the ethanol model by 62, 72 and 96%, and in the indometacin model by 34, 70 and 75%, respectively, as compared with misoprostol (50 microg kg(-1), p.o.), the reference compound that caused lesion suppression by 67% in ethanol model and by 72% against indometacin-induced ulceration. The ED50 of DDF in reducing gastric lesions induced by ethanol and indometacin (dose of the DDF that reduced the gastric lesion area by 50% in relation to the control value) was 50.87 and 61.56 mg kg(-1), respectively. Mechanistic studies were carried out at 100 mg kg(-1) DDF using the ethanol model. Compared with N-acetylcysteine (750 mg kg(-1), p.o.), a donor of sulfhydryls, DDF only partially replenished the ethanol-induced depletion of gastric mucosal NP-SH. Pretreatment with TRPV1 antagonist capsazepine (5 mg kg(-1), i.p.) or the non-selective cyclooxygenase inhibitor indometacin (10 mg kg(-1), p.o.) effectively blocked the gastroprotective effect of DDF (100 mg kg(-1)) against ethanol damage. Furthermore, the effect of DDF was significantly reduced in mice pretreated with L-NAME, or glibenclamide, the respective inhibitors of nitric oxide synthase and K+ ATP channel activation. These data provide evidence to show that DDF affords gastroprotection against gastric damage induced by ethanol and indometacin by different and complementary mechanisms, which include involvement of endogenous prostaglandins, nitric oxide release, the activation of TRPV1 receptor or K+ ATP channels, besides a sparing effect on NP-SH reserve.