PSMA-targeted combination brusatol and docetaxel nanotherapeutics for the treatment of prostate cancer.

Active targeting to cancer involves exploiting specific interactions between receptors on the surface of cancer cells and targeting moieties conjugated to the surface of vectors such that site-specific delivery is achieved. Prostate specific membrane antigen (PSMA) has proved to be an excellent target for active targeting to prostate cancer. We report the synthesis and use of a PSMA-specific ligand (Glu-NH-CO-NH-Lys) for the site-specific delivery of brusatol- and docetaxel-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles to prostate cancer. The PSMA targeting ligand covalently linked to PLGA-PEG3400 was blended with methoxyPEG-PLGA to prepare brusatol- and docetaxel-loaded nanoparticles with different surface densities of the targeting ligand. Flow cytometry was used to evaluate the impact of different surface densities of the PSMA targeting ligand in LNCaP prostate cancer cells at 15 min and 2 h. Cytotoxicity evaluations of the targeted nanoparticles reveal differences based on PSMA expression in PC-3 and LNCaP cells. In addition, levels of reactive oxygen species (ROS) were measured using the fluorescent indicator, H2DCFDA, by flow cytometry. PSMA-targeted nanoparticles loaded with docetaxel and brusatol showed increased ROS generation in LNCaP cells compared to PC-3 at different time points. Furthermore, the targeted nanoparticles were evaluated in male athymic BALB/c mice implanted with PSMA-producing LNCaP cell tumors. Evaluation of the percent relative tumor volume show that brusatol-containing nanoparticles show great promise in inhibiting tumor growth. Our data also suggest that the dual drug-loaded targeted nanoparticle platform improves the efficacy of docetaxel in male athymic BALB/c mice implanted with PSMA-producing LNCaP cell tumors.

Trajectories and tipping points of piñon-juniper woodlands after fire and thinning.

Piñon-juniper (PJ) woodlands are a dominant community type across the Intermountain West, comprising over a million acres and experiencing critical effects from increasing wildfire. Large PJ mortality and regeneration failure after catastrophic wildfire have elevated concerns about the long-term viability of PJ woodlands. Thinning is increasingly used to safeguard forests from fire and in an attempt to increase climate resilience. We have only a limited understanding of how fire and thinning will affect the structure and function of PJ ecosystems. Here, we examined vegetation structure, microclimate conditions, and PJ regeneration dynamics following ~20 years post-fire and thinning treatments. We found that burned areas had undergone a state shift that did not show signs of returning to their previous state. This shift was characterized by (1) distinct plant community composition dominated by grasses; (2) a lack of PJ recruitment; (3) a decrease in the sizes of interspaces in between plants; (4) lower abundance of late successional biological soil crusts; (5) lower mean and minimum daily soil moisture values; (6) lower minimum daily vapor pressure deficit; and (7) higher photosynthetically active radiation. Thinning created distinct plant communities and served as an intermediate between intact and burned communities. More intensive thinning decreased PJ recruitment and late successional biocrust cover. Our results indicate that fire has the potential to create drier and more stressful microsite conditions, and that, in the absence of active management following fire, there may be shifts to persistent ecological states dominated by grasses. Additionally, more intensive thinning had a larger impact on community structure and recruitment than less intensive thinning, suggesting that careful consideration of goals could help avoid unintended consequences. While our results indicate the vulnerability of PJ ecosystems to fire, they also highlight management actions that could be adapted to create conditions that promote PJ re-establishment.

Psychological Readiness to Return to Sport After Shoulder Instability.

¼ The shoulder is the most commonly dislocated joint in the body, representing 50% of all major joint dislocations. This injury occurs most commonly in contact sports and may be treated either nonoperatively (rest, immobilization, and physical therapy) or surgically.¼ Several factors contribute to an athlete's recovery after shoulder injury, including psychological readiness that has been identified as having a significant impact on athlete's rate of return to sport. The psychological readiness of athletes can be quantified using patient-reported outcome measures and psychological assessment tools.¼ Managing priorities and expectations, mood, social support, and confidence have all been identified as factors that affect readiness to return to play. Kinesiophobia was the most common factor reported in patients interviewed after arthroscopic Bankart repair.¼ Psychological interventions including cognitive behavioral therapy and mindfulness are aimed at reducing the effects of psychological factors and mood states by decreasing stress, anxiety, and kinesiophobia. These interventions may also increase the rates of return to sport after shoulder instability.

Droughting a megadrought: Ecological consequences of a decade of experimental drought atop aridification on the Colorado Plateau.

Global dryland vegetation communities will likely change as ongoing drought conditions shift regional climates towards a more arid future. Additional aridification of drylands can impact plant and ground cover, biogeochemical cycles, and plant-soil feedbacks, yet how and when these crucial ecosystem components will respond to drought intensification requires further investigation. Using a long-term precipitation reduction experiment (35% reduction) conducted across the Colorado Plateau and spanning 10 years into a 20+ year regional megadrought, we explored how vegetation cover, soil conditions, and growing season nitrogen (N) availability are impacted by drying climate conditions. We observed large declines for all dominant plant functional types (C3 and C4 grasses and C3 and C4 shrubs) across measurement period, both in the drought treatment and control plots, likely due to ongoing regional megadrought conditions. In experimental drought plots, we observed less plant cover, less biological soil crust cover, warmer and drier soil conditions, and more soil resin-extractable N compared to the control plots. Observed increases in soil N availability were best explained by a negative correlation with plant cover regardless of treatment, suggesting that declines in vegetation N uptake may be driving increases in available soil N. However, in ecosystems experiencing long-term aridification, increased N availability may ultimately result in N losses if soil moisture is consistently too dry to support plant and microbial N immobilization and ecosystem recovery. These results show dramatic, worrisome declines in plant cover with long-term drought. Additionally, this study highlights that more plant cover losses are possible with further drought intensification and underscore that, in addition to large drought effects on aboveground communities, drying trends drive significant changes to critical soil resources such as N availability, all of which could have long-term ecosystem impacts for drylands.

Attenuation of Seizures, Cognitive Deficits, and Brain Histopathology by Phytochemicals of Imperata cylindrica (L.) P. Beauv (Poaceae) in Acute and Chronic Mutant Drosophila melanogaster Epilepsy Models.

Imperata cylindrica is a globally distributed plant known for its antiepileptic attributes, but there is a scarcity of robust evidence for its efficacy. The study investigated neuroprotective attributes of Imperata cylindrica root extract on neuropathological features of epilepsy in a Drosophila melanogaster mutant model of epilepsy. It was conducted on 10-day-old (at the initiation of study) male post-eclosion bang-senseless paralytic Drosophila (parabss1) involved acute (1-3 h) and chronic (6-18 days) experiments; n = 50 flies per group (convulsions tests); n = 100 flies per group (learning/memory tests and histological examination). Administrations were done in 1 g standard fly food, per os. The mutant flies of study (parabss1) showed marked age-dependent progressive brain neurodegeneration and axonal degeneration, significant (P < 0.05) bang sensitivity and convulsions, and cognitive deficits due to up-regulation of the paralytic gene in our mutants. The neuropathological findings were significantly (P < 0.05) alleviated in dose and duration-dependent fashions to near normal/normal after acute and chronic treatment with extract similar to sodium valproate. Therefore, para is expressed in neurons of brain tissues in our mutant flies to bring about epilepsy phenotypes and behaviors of the current juvenile and old-adult mutant D. melanogaster models of epilepsy. The herb exerts neuroprotection by anticonvulsant and antiepileptogenic mechanisms in mutant D. melanogaster due to plant flavonoids, polyphenols, and chromones (1 and 2) which exert antioxidative and receptor or voltage-gated sodium ion channels' inhibitory properties, and thus causing reduced inflammation and apoptosis, increased tissue repair, and improved cell biology in the brain of mutant flies. The methanol root extract provides anticonvulsant and antiepileptogenic medicinal values which protect epileptic D. melanogaster. Therefore, the herb should be advanced for more experimental and clinical studies to confirm its efficacy in treating epilepsy.

The Fe-FeSi phase diagram at Mercury's core conditions.

Mercury's metallic core is expected to have formed under highly reducing conditions, resulting in the presence of significant quantities of silicon alloyed to iron. Here we present the phase diagram of the Fe-FeSi system, reconstructed from in situ X-ray diffraction measurements at pressure and temperature conditions spanning over those expected for Mercury's core, and ex situ chemical analysis of recovered samples. Under high pressure, we do not observe a miscibility gap between the cubic fcc and B2 structures, but rather the formation of a re-entrant bcc phase at temperatures close to melting. Upon melting, the investigated alloys are observed to evolve towards two distinct Fe-rich and Fe-poor liquid compositions at pressures below 35-38 GPa. The evolution of the phase diagram with pressure and temperature prescribes a range of possible core crystallization regimes, with strong dependence on the Si abundance of the core.

Sociodemographic factors associated with acceptance of COVID-19 vaccine and clinical trials in Uganda: a cross-sectional study in western Uganda.

BACKGROUND: Health experts agree that widespread use of safe and effective vaccines will rapidly contain the COVID-19 pandemic. The big question is whether these vaccines can easily be accepted by their end-users. Our study aimed at determining sociodemographic factors associated with acceptance of vaccines and clinical trials of COVID-19 in western Uganda. METHOD: A simplified snowball sampling technique was used to select 1067 respondents of 18-70 years in western Uganda using an online questionnaire from July to September 2020. Vaccine acceptability and risk perception were assessed using odds ratio at 95% confidence interval in R software version 3.6.3. RESULTS: There were 1067 participants in the study. The majority were males (73.2%) and age group 31-40 years (32.6%). The acceptance rate for COVID-19 vaccination was (53.6%; 572/1067) with those aged 18-20 years, males, elites at tertiary level of education (degree or diploma), students, Muslims, married, non-salary earners and rural dwellers having better odds and likeliness to accept vaccination. Only 44.6% (476/1067) showed interest in clinical trials among which; males, primary school leavers, students, Christians, un-married, respondents who didn't earn any salary and rural dwellers had better odds and likelihood to participate in clinical trials. CONCLUSION: There was a low level of vaccine acceptance and clinical trial interest in western Uganda. Minority groups in the study i.e., Muslims, students, primary school leavers, un-married rural dwellers among others showed more interest in vaccination and clinical trials. We anticipated fears in the larger part of this community that health experts need to address through reassurance of the community that vaccines are tested and that they are safe and important if we are to rapidly contain the COVID-19 pandemic.

Surgical Duration Implicated in Major Postoperative Complications in Total Hip and Total Knee Arthroplasty: A Retrospective Cohort Study.

INTRODUCTION: Total hip and knee arthroplasties are two of the most commonly performed orthopaedic surgeries and are expected to increase in incidence in the coming decades. We sought to examine whether the duration of these procedures is related to various postoperative complications using data from 2010 to 2017 from the American College of Surgeons National Surgical Quality Improvement Program database. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried for patients undergoing total hip and knee arthroplasty by their respective Current Procedural Terminology codes. Operation time was stratified into four quartiles with equal sample sizes in each quartile for total hip and knee arthroplasty separately. The first quartile of surgical times was used as the control to which the other three quartiles were compared. Multivariate logistic regression analysis was performed on all samples that accounted for possible covariates, totaling 119,076 patients for total hip and 189,297 for total knee arthroplasty. RESULTS: The third and fourth quartiles of total hip and total knee arthroplasty were markedly associated with higher incidences of wound complications, particularly infection and dehiscence. In addition, prolonged total hip arthroplasty was associated with a markedly higher rate of urinary tract infections for the third and fourth quartiles, and deep vein thrombosis in the fourth quartile. CONCLUSIONS: The surgical duration of total hip and knee arthroplasties is an independent risk factor for wound complications and several other important postoperative complications. Therefore, extensive preoperative planning and postoperative prophylactic measures should be performed to minimize patient morbidity and reduce hospital costs.

Effect of cognitive-behavioral therapy with music therapy in reducing physics test anxiety among students as measured by generalized test anxiety scale.

BACKGROUND: The study determined the effect of cognitive-behavioral therapy (CBT) with music in reducing physics test anxiety among secondary school students as measured by generalized test anxiety scale. METHODS: Pre-test post-test randomized control trial experimental design was adopted in this study. A total of 83 senior secondary students including male (n = 46) and female (n = 37) from sampled secondary schools in Enugu State, Nigeria, who met the inclusion criteria constituted participants for the study. A demographic questionnaire and a 48-item generalized test anxiety scale were used for data collection for the study. Subjects were randomized into treatment and control groups. The treatment group was exposed to a 12-week CBT-music program. Thereafter, the participants in the treatment group were evaluated at 3 time points. Data collected were analyzed using repeated measures analysis of variance. RESULTS: The participants who were exposed to CBT-music intervention program significantly had lower test anxiety scores at the post-treatment than the participants in the control group. Furthermore, the test anxiety scores of the participants in the CBT-music group were significantly lower than those in the control group at the follow-up measure. Thus, the results showed a significant effect of CBT with music in reducing physics test anxiety among secondary school students. CONCLUSION: We concluded that CBT-music program has a significant benefit in improving the management of physics test anxiety among secondary school students.

Impact of rational emotive occupational health coaching on work-related stress management among staff of Nigeria police force.

BACKGROUND: Empirical studies indicated that job-related stress is threatening the well-being of Nigerian public workers. The objective of this investigation was to examine the impact of REOHC for improving work-stress management among Staff of Nigeria Police Force in southeast Nigeria. METHOD: This is a pretest-posttest control group design study with follow-up. A total of 63 Nigerian police officers (randomized into one of 2 groups: n = 32 for treatment group, n = 31 for waitlist control group) completed the study. Two self-report questionnaire measuring organizational and operational stressors associated with police general well-being were used as outcome measures. The intervention group received a 12-week REBC manual intervention. The intervention and waitlisted groups were evaluated at 3-time points: Time1, Time2, and Time3. Statistical analyses were achieved using repeated-measures ANOVA. RESULTS: Results showed that there was no significant difference between the REOHC group and waiting-list control group in initial work-related stress management among staff of Nigerian Police Force. REOHC program had a significant effect on work-related stress management among staff of Nigerian Police Force when compared to their counterparts in the waiting-list control group. CONCLUSION: Therefore, REOHC program is a time-effective treatment approach for improving work-stress management among Staff of Nigeria Police Force in southeast Nigeria.

Randomized controlled evaluation of the effect of music therapy with cognitive-behavioral therapy on social anxiety symptoms.

OBJECTIVE: This study examined the effects of music therapy with cognitive behavioral therapy on social anxiety in a sample of schooling adolescents in south-east Nigeria. METHODS: We adopted a randomized controlled trial design involving a treatment group and a waiting-list control group. A total of 155 schooling adolescents served as the study sample. The sample size was ascertained using GPower software. A 12-week MTCBP manual for social anxiety was employed to deliver the intervention. Data analyses were completed using repeated measures analysis of variance. RESULTS: We found that social anxiety significantly decreased in the treatment group over time, whereas the waitlist control group showed no significant changes in social anxiety. Therefore, music therapy with cognitive-behavioral therapy was significantly beneficial in decreasing social anxiety symptoms of the treatment group. The follow-up assessment performed after 3 months revealed a significant reduction in social anxiety for the treatment group. CONCLUSION: The study, therefore, suggests that the use of music therapy with cognitive-behavioral therapy is significant in reducing social anxiety among schooling adolescents.

Versatile and Finely Tuned Albumin Nanoplatform based on Click Chemistry.

Albumin is one of the most attractive nanoplatforms for targeted imaging and drug delivery due to its biocompatibility and long circulation half-life. However, previously reported albumin-based nanoplatforms have shown inconsistent blood circulation half-life according to the modified methods, and the affecting factors were not well evaluated, which could hamper the clinical translation of albumin-based nanoplatforms. Herein, we developed a finely tuned click-chemistry based albumin nanoplatform (CAN) with a longer circulation half-life and an efficient tumor targeting ability. Methods: CAN was synthesized in two steps. First, albumin was conjugated with ADIBO-NHS (albumin-ADIBO) by reacting albumin with various molar ratios of ADIBO. The number of attached ADIBO moieties was determined using matrix-assisted laser desorption ionization time of flight (MALDI-TOF). Second, the desired modalities including azide-functionalized chelator, a fluorescence dye, and folate were incorporated into albumin-ADIBO using strain-promoted alkyne-azide cycloaddition reaction (SPAAC reaction). The biodistribution and targeting efficiency of functionalized CANs were demonstrated in mice. Results: The degree of functionalization (DOF) and resulting in vivo biodistribution was controlled precisely using the click chemistry approach. Specifically, the numbers of attached azadibenzocyclooctyne (ADIBO) moieties on albumin, the DOF, were optimized by reacting albumin with varying molar ratios of ADIBO with a high reproducibility. Furthermore, we developed a simple and efficient method to estimate the DOF using UV-visible spectrophotometry (UV-vis), which was further validated by matrix-assisted laser desorption ionization time of flight (MALDI-TOF). The biodistribution of CAN could be controlled by DOF, and CAN with an optimized DOF showed a long circulation half-life (> 18 h). CAN was further functionalized using a simple click chemistry reaction with an azide functionalized chelator, a fluorescence dye, and folate. 64Cu- and folate-labeled CAN (64Cu-CAN-FA) showed effective and specific folate receptor targeting in vivo, with an over two-fold higher uptake than the liver at 24 h post-injection. Conclusions: Our development from the precisely controlled DOF demonstrates that an optimized CAN can be used as a multifunctional nanoplatform to obtain a longer half-life with radioisotopes and ligands, and provides an effective method for the development of albumin-based tumor theranostic agents.

Efficacy of prison-based cognitive behavioral rehabilitation intervention on violent sexual behaviors among sex offenders in Nigerian prisons.

BACKGROUND/OBJECTIVE: Evidence showed that reoffending habits are increasing among offenders with violent sexual behaviors. Given the recidivism rates, a psychotherapeutic intervention becomes imperative. This study examined the efficacy of prison-based cognitive behavioral rehabilitation intervention (PCBRI) on violent sexual behaviors among sex offenders in Nigerian prisons. METHOD: A total of45 participants were the sample size. Compulsive Sexual Behavior Inventory and Hypersexual Behavior Inventory were employed in assessing the participants at 3 points. Using a simple random allocation sequence, 23 participants were exposed to PCBRI programme and 22 participants allocated to control condition. The data obtained were analyzed using repeated measures 2-way analysis of variance. RESULTS: Results indicated a significant effect of the treatment on violent sexual behaviors among sex offenders in Nigerian prisons exposed to the PCBRI programme when compared to the no-intervention group. Result also showed a significant interaction effect of time and group on sex offenders with violent sexual behaviors. Follow-up tests showed significant decrease in violent sexual behaviors after 6 months for the PCBRI group in comparison to the control group. CONCLUSION: This study concluded that PCBRI approach is a type of psychotherapy that reduces violent sexual behaviors among sex offenders in Southeast Nigeria.

Impacts of cognitive-behavioral intervention on anxiety and depression among social science education students: A randomized controlled trial.

BACKGROUND: Anxiety is a common disorder which refers to a significant and persistent fear of one or more social or performance situations. This study investigated the impacts of cognitive-behavioral intervention on anxiety and depression among undergraduate students enrolled in social science education programs at public universities in the Southeast Nigeria. METHODS: Participants were 55 undergraduate students enrolled in social science education programs at public universities in the Southeast Nigeria. The adequacy of the sample size used was determined using GPower software. Cognitive-behavioral treatment manuals on anxiety and depression were used to deliver the intervention. Data analyses were completed using repeated measures analysis of variance. RESULTS: Results indicated a significant positive impact of cognitive-behavioral intervention on anxiety and depression among social science education students exposed to the cognitive-behavioral intervention when compared to the waitlisted group. Results also showed that there was a significant time × group interaction for anxiety and depression. Follow-up tests showed that significant reduction in anxiety and depression persisted after 3 months for the cognitive-behavioral intervention group in comparison to the waitlisted control group. CONCLUSION: We concluded that cognitive-behavioral intervention was a successful intervention which decreased the symptoms of anxiety and depression in social science education students who participated in the study. Additional studies are recommended to further corroborate the influence of cognitive-behavioral intervention in the reduction of anxiety and depressive symptoms in the Nigerian undergraduate student population.

Manufacturing Simple and Inexpensive Soil Surface Temperature and Gravimetric Water Content Sensors.

Quantifying temperature and moisture at the soil surface is essential for understanding how soil surface biota respond to changes in the environment. However, at the soil surface these variables are highly dynamic and standard sensors do not explicitly measure temperature or moisture in the upper few millimeters of the soil profile. This paper describes methods for manufacturing simple, inexpensive sensors that simultaneously measure the temperature and moisture of the upper 5 mm of the soil surface. In addition to sensor construction, steps for quality control, as well as for calibration for various substrates, are explained. The sensors incorporate a Type E thermocouple to measure temperature and assess soil moisture by measuring the resistance between two gold-plated metal probes at the end of the sensor at a depth of 5 mm. The methods presented here can be altered to customize probes for different depths or substrates. These sensors have been effective in a variety of environments and have endured months of heavy rains in tropical forests as well as intense solar radiation in deserts of the southwestern U.S. Results demonstrate the effectiveness of these sensors for evaluating warming, drying, and freezing of the soil surface in a global change experiment.

The Adult Calfactant in Acute Respiratory Distress Syndrome Trial.

BACKGROUND: Surfactant has been shown to be dysfunctional in ARDS, and exogenous surfactant has proven effective in many forms of neonatal and pediatric acute lung injury (ALI). In view of the positive results of our studies in children along with evidence that surfactant-associated protein B containing pharmaceutical surfactants might be more effective, we designed a multiinstitutional, randomized, controlled, and masked trial of calfactant, a calf lung surfactant, in adults and children with ALI/ARDS due to direct lung injury. METHODS: Adult subjects within 48 h of initiation of mechanical ventilation for direct ARDS were randomized to receive up to three interventions with instilled calfactant vs air placebo. The primary outcome was 90-day all-cause mortality. RESULTS: Three hundred seventeen subjects were enrolled, 308 of whom could be evaluated. There were no significant baseline differences between groups. Calfactant administration was not associated with improved survival, lengths of stay, or oxygenation. Calfactant instillation was frequently associated with transient hypoxia and hypotension. The study was stopped at the first interim analysis at the sponsor's request. CONCLUSIONS: Administration of calfactant was not associated with improved oxygenation or longer-term benefits relative to placebo in this randomized, controlled, and masked trial. At present, exogenous surfactant cannot be recommended for routine clinical use in ARDS. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00682500; URL: www.clinicaltrials.gov.