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Robotic assistance has become essential for patients with motor dysfunction, and compared to passive training, robot-assisted training with subjective locomotion intentions promotes better health recovery. In this review, the authors briefly mention robot-assisted restoration of musculoskeletal health as a pressing new field in rehabilitation. Robotic application to restore musculoskeletal health can enhance rehabilitation, but must be used according to well-defined scientific protocols. The field of robotic therapy poses challenges for both technology and clinical practice.

Statins are widely prescribed medications that inhibit 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG CoA) reductase and therefore reduce cholesterol synthesis. Given the key role of cholesterol in cancer, statins may therefore have anticancer activities. However, clinical studies investigating the association between statin usage and cancer development have been few and inconsistent. A recent study from Maeda-Minami and colleagues found a significant, though modest, decrease in cancer risk among statin users. However, does this finding mean statin usage directly reduces cancer risk or is merely associated with reduced cancer risk? This editorial analyzes Maeda-Minami and colleagues’ study to provide commentary on statin's proposed role in preventing cancer.See related article, p. 37

Excitotoxicity in the brain is a causal factor in several neurological and neurodegenerative disorders. Excitatory amino acid transporter 2 (EAAT2), an astrocytic glutamate transporter involved in the clearance of80% of synaptic glutamate, is considered a therapeutically relevant target for excitotoxicity. We have previously designed GT951, an activator of EAAT2 with nanomolar efficacy but limited in vivo bioavailability. In this study, a pharmacophore-based screening and optimization resulted in the design of GTS467 and GTS511. GTS467 and GTS511 have low nanomolar efficacy in the glutamate uptake assay. Pharmacokinetic profiles (PK) of GTS511 show a6 h half-life and higher bioavailability in plasma and the brain under all three routes of administration in rats. Similarly, GTS467 has high oral bioavailability (80-85%) in the brain and plasma with a1 h half-life under all three dosing routes. These encouraging efficacy and PK profiles suggest that GTS511 and GTS467 can be further developed to treat neurological disorders caused by excitotoxicity.

Objective To improve prostate cancer screening for high-risk men, we developed an early detection clinic for patients at high genetic risk of developing prostate cancer. Despite the rapidly growing understanding of germline variants in driving aggressive prostate cancer and the increased availability of genetic testing, there is little evidence surrounding how best to screen these men. Methods We are reporting on the first 45 patients enrolled, men between the ages of 35–75, primarily with known pathogenic germline variants in prostate cancer susceptibility genes. Screening consists of an intake lifestyle survey, PSA, DRE, and SelectMDx urine assay. A biopsy was recommended for any of the following indications: 1) abnormal DRE, 2) PSA above threshold, or 3) SelectMDx above threshold. The primary outcomes were number needed to screen, and number needed to biopsy to diagnose a patient with prostate cancer. Results Patients enrolled in the clinic included those with BRCA1 (n=7), BRCA2 (n=16), Lynch Syndrome (n=6), and CHEK2 (n = 4) known pathogenic germline variants. The median age and PSA were 58 (range 35–71) and 1.4 ng/ml (range 0.1–11.4 ng/ml), respectively. 12 patients underwent a prostate needle biopsy and there were 4positive biopsies for prostate cancer. Conclusion These early data support the feasibility of opening a dedicated clinic for men at high genetic risk of prostate cancer. This early report on the initial enrollment of our long-term study will help optimize early detection protocols and provide evidence for personalized prostate cancer screening in men with key pathogenic germline variants.

Indications for germline testing in prostate cancer patients have expanded substantially over the past decade. With a near-universal shortage of genetic counselors and increasing demand, increased access to genetic counseling is crucial. We sought to prospectively implement and assess a clinician-led approach to genetic counseling and testing.Patients with metastatic or localized prostate cancer meeting National Comprehensive Cancer Network® criteria for consideration of genetic testing were offered pre-test genetic counseling by their urologist or medical oncologist as part of their routine clinical care and concurrently approached for enrollment in the Germline Genetics in Prostate Cancer Study. Consented patients filled out a post-counseling survey using validated instruments to assess the quality of counseling. For patients who elected to undergo genetic testing, an additional validated questionnaire was completed following disclosure of results. The primary outcome was the proportion of patients undergoing testing, with a target60% of patients. The secondary outcome was overall satisfaction with counseling, with a target85% of patients.A total of 275 patients enrolled, and 203 patients elected to undergo genetic testing. Post-counseling surveys were obtained from 265 patients, and post-genetic testing surveys were obtained from 132 patients. Patient satisfaction was high, with 98% of patients reporting being satisfied with the overall quality of pre-test counseling, and 74% of patients elected to undergo genetic testing.These results support the effectiveness of clinician-led genetic counseling in prostate cancer. With clinician training, this approach can be utilized to expand access to appropriate germline genetic testing.

461 Background: Prior studies suggest that white light cystoscopy (WLC) alone can fail to detect cases of non-muscle invasive bladder cancer (NMIBC) compared to blue light cystoscopy (BLC). We describe bladder cancer outcomes and the impact of BLC among NMIBC patients in an equal access setting. Methods: A total of 378 NMIBC patients within the Veterans Affairs system that had a CPT code for BLC from December 1, 2014 to December 31, 2020 were assessed. We determined recurrence rates and time to recurrence prior to BLC (i.e. after previous WLC if available) and following BLC. We used the Kaplan-Meier method to estimate event-free survival and Cox regression to determine the association between race and recurrence, progression, and overall survival. Results: Of 378 patients with complete data, 43 (11%) were Black and 300 (79%) White. Median follow-up was 40.7 months from bladder cancer diagnosis. There were 194 (51%) patients with either TaHG or T1 without CIS; 52 (14%) had CIS with or without TaHG or T1; and 127 (34%) had TaLG only. A total of 239 (63%) patients received BCG at any point during the study. Median time to first recurrence following BLC was longer compared to WLC alone (40 (33-NE) vs. 26 (17-39) months). The risk of recurrence was significantly lower following BLC (Hazard Ratio (HR) 0.70; 95% Confidence Interval (CI) 0.54-0.90). There was no significant difference in recurrence (Hazard Ratio (HR) 0.83; 95% Confidence Interval (CI) 0.48-1.43), progression (HR 1.46; 95% CI 0.45-4.74), and overall survival (HR 0.69; 95% CI 0.29-1.65) following BLC by Black vs. White race. Conclusions: In this study from an equal access setting in the VA, we observed significantly decreased risk of recurrence and prolonged time interval to recurrence following BLC compared to WLC alone. There was no difference in any bladder cancer outcomes by race.

INTRODUCTION AND OBJECTIVE:Global health surgical programs generally provide support through hands on surgical workshops. The COVID-19 pandemic has significantly impacted domestic and international...

Amyotrophic lateral sclerosis (ALS) is a late-onset, neurodegenerative disease associated with the loss of motor neurons in the spinal cord, brain stem and primary motor cortex. Deficit in the motor function is one of the clinical features of this disease. However, the association between adverse morphological alterations in the spinal motor neurons and motor deficit in sporadic ALS (SALS) is still debated. The present study has sought to investigate the effects of serial intrathecal injections of ALS-CSF into rat pups, at post-natal (P) days 3, 9 and 14, on the motor neuronal (MN) morphology at the cervical and lumbar levels of the spinal cord at P16 and P22. The present study used Cresyl violet and Golgi-Cox staining methods to determine the progressive changes in the morphology of spinal MNs in both cervical and lumbar extensions. The study found a loss of motor neurons in the spinal cord (36% for P16 in cervical and 41.7% in P16 lumbar and 49.57% for P22 cervical and 44.63% for P22 lumbar) and reduced choline acetyl transferase (ChAT) expression after repeated infusion of ALS-CSF. Significant increase in the soma area was also found in ALS-CSF rats (around 21% in P22 cervical and 26.4% in P22 lumbar). Soma hypertrophy was associated with increased dendritic arborization of MNs at both cervical and lumbar levels of the spinal cord. The data also showed a direct correlation between ALS-CSF induced changes in the MN number in the spinal cord and motor behavioral deficits. The loss of MNs, reduced ChAT, changes in soma and dendritic morphology with declined rotarod performance, thus, confirming the pathological phenotypes as seen in ALS patients.

Carbonate hosted intermetallic compound in the Umarvaniyan area is localized within the intensively sheared (mylonitised) dolomite in a NW–SE shear zone (~15 km), belongs to Salumber Ghatol metallogenic belt, in Debari Group of Aravalli Craton, Rajasthan, India. It is characterized by extensive silicification and ferruginisation with hematite, goethite, magnetite and native gold specks. The intermetallic compound within the dolomite is composed of varying proportion of Cu–Zn–Ni–Os–Fe which has been detected by electron probe microanalysis (EPMA) study. The EMPA (WDS) results of the intermetallic compounds also reveal occurrences of intermetallic compounds of Cu–Zn–Ni–Os–Fe and native Au. The occurrence of these non-separable compounds is probably because these metals were formed at very high temperatures and in reducing condition during the evolving shear with low oxygen and low sulfur fugacity. The fast cooling effect thereafter probably made the geochemical environment least conducive for reaction between Cu/Zn/Ni and sulphur or oxygen.

74 Background: Increased mortality from urologic cancers coupled with an aging population has resulted in patient care becoming more specialized to improve patient outcomes. Though family history, lifestyle behaviors, and genetics are all used to determine risk and treatment, there is a knowledge gap of whether mental illness (MI) should also be considered. Therefore, this study seeks to determine whether hospitalizations of urologic cancers plus MIs are associated with increased all-cause mortality, length of hospital stay (LOS), costs of hospitalization and nosocomial infection rates. Methods: Inpatient data from 2016-2017 was obtained from the National Inpatient Sample database. This included all hospitalizations with at least one diagnosis of urologic cancer including prostate, bladder, kidney, renal pelvis, ureteral, urethral, testicular, and penile cancers. MIs of interest were depression, anxiety, substance abuse, and schizophrenia and related disorders. Data analysis and regression models were performed using SPSS Statistics. Reported odds ratios and significance values were controlled for Age, Sex, Income, Race, Insurance, Location, Mortality Risk, and Illness Severity. Results: There were 146,706 hospitalizations involving urologic cancers between 2016-2017. For these hospitalizations, depression and anxiety were associated with a decreased likelihood of death, and all MIs were associated with increased LOS. For hospitalizations involving prostate cancer, Depression and Substance Abuse were associated with decreased likelihood of death (all-causes). Hospitalizations involving kidney cancer had increased total charges and increased LOS. Hospitalizations involving bladder cancer were associated with decreased likelihood of death, and increased LOS for all MIs except, notably, those with substance abuse. Penile Cancer hospitalizations coded for anxiety showed increased LOS, and testicular cancer hospitalizations coded for substance abuse had increased likelihood of death. Conclusions: MIs can affect hospitalization outcomes of patients with urologic cancer differently based on the type of urologic cancer. Interestingly, our analysis showed that Depression was associated a decreased likelihood of death in hospitalizations coded for Prostate Cancer and Bladder Cancer. Though unexpected, we hypothesize that this finding may be partially due to implicit bias from healthcare providers that lead to enhanced care (e.g. increased patient monitoring, better support from auxiliary units such as Social Work). However, there is an absence of research in substantiating this claim. Further research is warranted to better assess the effect of Depression on the mortality of Urologic Cancer patients, and on how to best incorporate mental health status in the overall management of these patients.

Land surface temperature (LST) shows negative correlation with the Normalized Difference Water Index (NDWI). Variability in the degree of correlation between LST and NDWI is ascribed to the physical character of specific geological material. Northwest India exhibits various landforms with different geological materials and has been broadly classified into four zones. Structural ridges of Aravalli Mountain of different rock compositions show strong variability both in NDWI (range 1.154, SD = 0.0599) and in LST (range 24 °C and SD = 2.54). Negative LST–NDWI correlation in this sector is partially linear. Western Thar Desert, having homogenous silica sand of lower emissivity shows least variability in its NDWI (range 0.88, SD = 0.027) and moderate variability in its LST (20 °C, SD = 2.389). Strong negative correlation of LST with NDWI is exhibited here. Band ratio Silica map in this sector shows strong positive correlation with LST. The eastern part of the Thar desert with mixed rocky knobs, and wind-blown sand shows low variability in NDWI (range 0.85) as well as LST (range 15 °C). Area in Indus–Bias–Sutlej River basin, dominated with fluvial sediments with lesser amount of windblown sediments, show low variability of NDWI (0.85) and moderate variability of LST (range 23 °C). In the areas, around Luni river higher NDWI trend is recorded, which is unrelated to present drainage trends indicating presence of palaeo-drainage. In addition, high NDWI and high LST bearing linear zones at places are interpreted as structural lineaments/faults based on pattern, moisture content and thermal high.

Until recently the role of germline genetics in prostate cancer care was not well defined. While important questions remain, we reviewed the current understanding of germline genetic alterations related to prostate cancer. We discuss the clinical implications for genetic counseling, genetic testing, early detection and treatment in men with these mutations.We searched PubMed® for English language articles published since 2001 with the key words "germline mutations," "BRCA," "family history" or "prostate cancer genetics." We also used relevant data from websites, including the Centers for Medicare and Medicaid Services, National Comprehensive Cancer Network®, Bureau of Labor Statistics and National Society of Genetic Counselors websites.A number of germline mutations in DNA damage repair genes ( BRCA1, BRCA2, CHEK2, ATM and PALB2) and in DNA mismatch repair genes ( MLH1, MSH2, MSH6 and PMS2) can drive the development of prostate cancer. Careful genetic counseling coupled with multipanel gene testing can help identify men with these mutations and provide enhanced understanding of the disease risk. Cascade testing of family members can then have an impact extending well beyond the index patient. In men with a pathogenic germline mutation the optimal early detection paradigm is not well defined. Data from the IMPACT study ( ClinicalTrials.gov NCT00261456) that the cancer detection rate is substantially elevated in BRCA1 and BRCA2 carriers at prostate specific antigen greater than 3 ng/ml has helped establish the importance of close prostate specific antigen screening in these men. Additionally, BRCA2 and likely other DNA damage repair mutations are associated with aggressive disease, although it is not yet clear how this impacts localized disease management. However, there is strong evidence that patients with metastatic, castration resistant prostate cancer who have DNA damage repair defects respond positively to targeting PARP enzymes. In many cancers there is also evidence that patients with an increased tumor mutational burden, such as in Lynch syndrome, are particularly sensitive to immune checkpoint inhibitors.Emerging evidence supports the implementation of germline genetic counseling and testing as a key component of prostate cancer management. Further research is needed to elucidate the clinical significance of lesser known germline mutations and develop optimal screening, early detection and treatment paradigms in this patient population.