Insight to urology patients' preferences regarding telemedicine.

INTRODUCTION: Due to COVID-19, telemedicine has become a common method of healthcare delivery. Our goal was to evaluate urology patients' satisfaction with telemedicine, examine patient preferences, and identify opportunities for improvement in readiness, access, and quality of care. MATERIALS AND METHODS: A total of 285 adult urology patients who completed at least one telemedicine visit from September to December 2020 were eligible. A paper survey was disseminated by postal mail with an option to complete electronically. Those who returned completed surveys received a $15 gift card. RESULTS: Seventy-six subjects completed the survey (response rate of 27%). The most common age bracket of the respondents was 70-79 years (37%). Readiness - To prepare, many subjects (49%) read the provided instructions. Most (91%) thought they were adequately prepared. A majority (82%) were satisfied with the ease of set up. Access - Types of visits included established patients (71%), new patient visits (17%), and postoperative visits (9%). Most respondents (84%) did not have difficulty accessing the visit. Quality of care - All respondents were satisfied with the length of visit, and 90% were satisfied with the overall experience. Patient preferences - Compared to office visits, most patients found telemedicine equal or superior in several areas. Preference to utilize telemedicine in the future was dependent on the nature of the complaint, length of their drive and their schedule. CONCLUSIONS: Patients reported high levels of satisfaction and a willingness to engage with telemedicine visits. To minimize future technical disruptions, we offer mock telehealth visits before their scheduled appointment and improved our clinicians' work flow.

An Enhanced Audiologic Protocol for Early Identification of Conductive Hearing Loss in Patients with Cleft Palate.

OBJECTIVE: To characterize the onset and prevalence of conductive hearing loss (CHL) in pediatric patients with cleft palate (CP) prior to palatoplasty with an enhanced audiologic protocol. DESIGN: Retrospective cohort study. SETTING: Multidisciplinary cleft and craniofacial clinic at a tertiary care center. PATIENTS: Patients with CP who received audiologic workup pre-operatively. Patients with bilateral permanent hearing loss, expiration prior to palatoplasty, or no pre-operative data were excluded. INTERVENTIONS: Patients with CP born February 2019 to November 2019 who passed newborn hearing screening (NBHS) received audiologic testing at 9 months of age (standard protocol). Patients born December 2019 to September 2020 underwent testing prior to 9 months of age (enhanced protocol). MAIN OUTCOME MEASURES: Age of identification of CHL in patients after implementation of the enhanced audiologic protocol. RESULTS: The number of patients who passed their NBHS in the standard protocol (n = 14, 54%) and the enhanced protocol (n = 25, 66%) did not differ. Infants who passed their NBHS, but demonstrated hearing loss on subsequent audiologic testing did not differ between enhanced (n = 25, 66%) and standard cohort (n = 14, 54%). Of patients who passed NBHS in the enhanced protocol, 48% (n = 12) had CHL identified by 3 months, and 20% (n = 5) by 6 months of age. With the enhanced protocol, patients who did not undergo additional testing post NBHS significantly dropped from 44.9% (n = 22) to 4.2% (n = 2) (P < .0001). CONCLUSION: Even with passed NBHS, CHL is still present for infants with CP pre-operatively. Earlier and more frequent testing for this population is recommended.

Oncological and functional outcomes in patients over 70 years of age treated with robotic radical prostatectomy: a propensity-matched analysis.

PURPOSE: The aim of this study was to report on the safety (complications) and efficacy (oncological and functional outcomes) of robot-assisted radical prostatectomy (RARP), performed at our institution, in patients aged over 70. PATIENTS AND METHODS: Review of our prospectively collected database [Cancer Information Systems (CAISIS)] identified two hundred and fifteen (215) patients, aged > 70, who underwent RARP for localized prostate cancer between July 2003 and August 2017. A propensity score-matched analysis, with multiple covariates, was performed to stratify the patients into Age ≤ 70 and Age > 70 comparison groups. RESULTS: Apart from Age (mean ± SD years: 73.5 ± 2.1 vs 59.5 ± 5.9, p < 0.0001) and nerve-sparing status, the two groups were evenly matched for all covariates (p values > 0.05). Median follow-up was 10.6 years. There were no 90-day mortalities in either group. Minor complications (Clavien ≤ 2) were more common in the Age > 70 group (p = 0.0002). Operating room time (p = 0.83), length of hospital stay (p = 0.06) and catheterization duration (p = 0.13) were similar. On final pathology, a higher pT stage (p < 0.0001) and pN1 (p = 0.003) were observed in the Age > 70 group. However, this did not translate adversely into higher rates of positive surgical margin (p = 0.41) or biochemical relapse (p = 0.72). Allowing for the follow-up duration (median 10.6 years), cancer-specific survival was marginally significant (p = 0.05) with an observed lower rate in the Age > 70 group. In terms of functional outcomes, post-operative erectile dysfunction and pad-free continence were significantly better in the younger cohort (p < 0.0001). CONCLUSIONS: Robot-assisted radical prostatectomy should not be denied to those over 70 years solely on the basis of age. Older men need to be counseled about the likelihood of encountering higher-risk features on final pathology and that their functional outcomes may be worse compared to a younger person.

Umbelliferone and esculetin protect against N-nitrosodiethylamine-induced hepatotoxicity in rats.

N-nitrosodiethylamine (NDEA), a nitrosamine compound, is known to cause liver damage through the generation of reactive oxygen species (ROS), resulting in oxidative damage to macromolecules such as DNA, and the consequent development of cancer. The present study examines the protective effects of two antioxidant coumarin compounds umbelliferone (Umb) and esculetin (Esc) against NDEA-induced hepatotoxicity when administered in the diet to male Wistar rats. The results show that treatment with Umb (0.5% w/w) and Esc (0.5% w/w) in the diet for 7 days significantly attenuates NDEA-induced liver damage, lowering serum alanine transaminase (ALT) levels, decreasing hepatic lipid peroxidation, and restoring total glutathione levels. To investigate the mechanism for the observed protective effect, the levels of the key protective enzymes NAD(P)H: quinone oxidoreductase 1 (NQO1), heme oxygenase (HO1), and glutathione S-transferase Pi (GSTP1) were measured by Western blotting following Umb and Esc administration. The results showed that Umb and Esc administration significantly increased the expression of NQO1 by 3.6- and 2.7-fold, HO1 by 2.7- and 3.2-fold, and GSTP1 by 2.8- and 3.2-fold, respectively. In conclusion, Umb and Esc are capable of protecting liver from NDEA-induced hepatotoxicity, and this is associated with the induction of protective enzymes.

Prepubertal-Onset Vulvar Lichen Sclerosus: The Importance of Maintenance Therapy in Long-Term Outcomes.

BACKGROUND: There is sufficient published data on induction treatment with potent topical corticosteroid (TCS) in childhood vulvar lichen sclerosus (VLS) but limited data on long-term management. VLS has been shown to extend beyond menarche and repercussions of suboptimal long-term control may be devastating and permanent. This single-center retrospective study reviewed outcomes of long-term treatment using individualized regimens with target outcome of complete objective normality. METHODS: Forty-six girls with prepubertal-onset VLS were studied for demographic data, previous treatment, induction and maintenance treatment, clinical response and compliance. Photographic records were available for all patients. The cohort was divided into two groups: adherent (using treatment all or most of the time) and non-adherent (using treatment some or less of the time). RESULTS: Twenty-six patients (56%) had received prior treatment however only three had achieved disease control using daily potent TCS. Twelve patients (26%) had scarring on presentation. All achieved initial objective disease suppression with induction treatment using potent TCS. Thirty-one of 33 adherent patients (93.93%) sustained complete disease remission with no progression or scarring. In contrast, 1 of the 13 nonadherent patients (8%) achieved complete disease remission (p < 0.001), 9 of the 13 (69.23%) experienced disease progression (p < 0.001) and 3 of the 13 (23%) developed scarring during follow-up. Those with established scarring on presentation did not recover with treatment. CONCLUSION: Our data support previous studies regarding initial treatment with potent TCS but additionally suggest maintenance treatment with individualized regimens that achieve objective normality in addition to symptom control provide optimal outcomes.

Illness absences among beryllium sensitized workers.

OBJECTIVES: This study examined absence rates among US Department of Energy workers who had beryllium sensitization (BeS) or were diagnosed with chronic beryllium disease (CBD) compared with those of other workers. METHODS: We used the lymphocyte proliferation test to determine beryllium sensitivity. In addition, we applied multivariable logistic regression to compare absences from 2002 to 2011 between workers with BeS or CBD to those without, and survival analysis to compare time to first absence by beryllium sensitization status. Finally, we examined beryllium status by occupational group. Results. Fewer than 3% of the 19,305 workers were BeS, and workers with BeS or CBD had more total absences (odds ratio [OR] = 1.31; 95% confidence interval [CI] = 1.18, 1.46) and respiratory absences (OR = 1.51; 95% CI = 1.24, 1.84) than did other workers. Time to first absence for all causes and for respiratory conditions occurred earlier for workers with BeS or CBD than for other workers. Line operators and crafts personnel were at increased risk for BeS or CBD. Conclusions. Although not considered "diseased," workers with BeS have higher absenteeism compared with nonsensitized workers.

Circulating plakin autoantibodies in a patient with erythema multiforme major: are they pathogenic or a manifestation of epitope spreading?

Erythema multiforme is a well-recognised entity but its pathogenesis remains elusive. Theories hypothesise a cell-mediated immune pathogenesis, however recent case reports have observed autoantibodies to the plakin family of proteins, suggesting a role for the humoral immune system. We present a case of erythema multiforme major with circulating desmoplakin autoantibodies in a 36-year old woman who was previously diagnosed with pemphigoid gestationis. The close correlation between the concentration of these autoantibodies and the severity of clinical disease strongly suggests a pathogenic role in her disease. As previous case reports have proposed, these autoantibodies may be directly pathogenic. Alternatively, the epiphenomenon of epitope spreading must be considered in the subset of patients with erythema multiforme major.

Importance of on-farm research for validating process-based models of climate-smart agriculture.

Climate-smart agriculture can be used to build soil carbon stocks, decrease agricultural greenhouse gas (GHG) emissions, and increase agronomic resilience to climate pressures. The US recently declared its commitment to include the agricultural sector as part of an overall climate-mitigation strategy, and with this comes the need for robust, scientifically valid tools for agricultural GHG flux measurements and modeling. If agriculture is to contribute significantly to climate mitigation, practice adoption should be incentivized on as much land area as possible and mitigation benefits should be accurately quantified. Process-based models are parameterized on data from a limited number of long-term agricultural experiments, which may not fully reflect outcomes on working farms. Space-for-time substitution, paired studies, and long-term monitoring of SOC stocks and GHG emissions on commercial farms using a variety of climate-smart management systems can validate findings from long-term agricultural experiments and provide data for process-based model improvements. Here, we describe a project that worked collaboratively with commercial producers in the Midwest to directly measure and model the soil organic carbon (SOC) stocks of their farms at the field scale. We describe this study, and several unexpected challenges encountered, to facilitate further on-farm data collection and the creation of a secure database of on-farm SOC stock measurements.

Color changing bioadhesive barrier for peripherally inserted central catheters.

Bacteria migration at catheter insertion sites presents a serious complication (bacteraemia) with high mortality rates. One strategy to mediate bacteraemia is a physical barrier at the skin-catheter interface. Herein a colorimetric biosensor adhesive (CathoGlu) is designed and evaluated for both colorimetric detection of bacterial infection and application as a bacteria barrier. The design intent combines viscous, hydrophobic bioadhesive with an organic pH indicator (bromothymol blue). Visual observation can then distinguish healthy skin at pH = ∼5 from an infected catheter insertion site at pH = ∼8. The liquid-to-biorubber transition of CathoGlu formulation occurs via a brief exposure to UVA penlight, providing an elastic barrier to the skin flora. Leachates from CathoGlu demonstrate no genotoxic and skin sensitization effect, assessed by OECD-recommended in vitro and in chemico assays. The CathoGlu formulation was found non-inferior against clinically approved 2-octyl-cyanoacrylate (Dermabond™), and adhesive tape (Micropore™) within an in vivo porcine model. CathoGlu skin adhesive provides new opportunities to prevent sepsis in challenging clinical situations.

Third mortality follow-up of the Mallinckrodt uranium processing workers, 1942-2019.

INTRODUCTION: Mallinckrodt Chemical Works was a uranium processing facility during the Manhattan Project from 1942 to 1966. Thousands of workers were exposed to low-dose-rates of ionizing radiation from external and internal sources. This third follow-up of 2514 White male employees updates cancer and noncancer mortality potentially associated with radiation and silica dust. MATERIALS AND METHODS: Individual, annualized organ doses were estimated from film badge records (n monitored = 2514), occupational chest x-rays (n = 2514), uranium urinalysis (n = 1868), radium intake through radon breath measurements (n = 487), and radon ambient measurements (n = 1356). Silica dust exposure from pitchblende processing was estimated (n = 1317). Vital status and cause of death determination through 2019 relied upon the National Death Index and Social Security Administration Epidemiological Vital Status Service. The analysis included standardized mortality ratios (SMRs), Cox proportional hazards, and Poisson regression models. RESULTS: Vital status was confirmed for 99.4% of workers (84.0% deceased). For a dose weighting factor of 1 for intakes of uranium, radium, and radon decay products, the mean and median lung doses were 65.6 and 29.9 mGy, respectively. SMRs indicated a difference in health outcomes between salaried and hourly workers, and more brain cancer deaths than expected [SMR: 1.79; 95% confidence interval (CI): 1.14, 2.70]. No association was seen between radiation and lung cancer [hazard ratio (HR) at 100 mGy: 0.93; 95%CI: 0.78, 1.11]. The relationship between radiation and kidney cancer observed in the previous follow-up was maintained (HR at 100 mGy: 2.07; 95%CI: 1.12, 3.79). Cardiovascular disease (CVD) also increased significantly with heart dose (HR at 100 mGy: 1.11; 95%CI: 1.02, 1.21). Exposures to dust ≥23.6 mg/m3-year were associated with nonmalignant kidney disease (NMKD) (HR: 3.02; 95%CI: 1.12, 8.16) and kidney cancer combined with NMKD (HR: 2.46; 95%CI: 1.04, 5.81), though without evidence of a dose-response per 100 mg/m3-year. CONCLUSIONS: This third follow-up of Mallinckrodt uranium processors reinforced the results of the previous studies. There was an excess of brain cancers compared with the US population, although no radiation dose-response was detected. The association between radiation and kidney cancer remained, though potentially due to few cases at higher doses. The association between levels of silica dust ≥23.6 mg/m3-year and NMKD also remained. No association was observed between radiation and lung cancer. A positive dose-response was observed between radiation and CVD; however, this association may be confounded by smoking, which was unmeasured. Future work will pool these data with other uranium processing worker cohorts within the Million Person Study.

Increasing Diversity, Equity, and Inclusion in Urology Residency Recruitment: Recommendations From the Society of Women in Urology.

OBJECTIVE: To provide a framework for diversifying the urologic workforce through residency recruitment by integrating principles of diversity, equity, and inclusion (DEI) into program mission and values, application review, and interview process. MATERIALS AND METHODS: For this narrative review, the Society of Women in Urology Advancing DEI in Urology Residency Recruitment Task Force identified 4 areas for incorporating DEI into residency recruitment: defining a residency program's mission and values, holistic application review, an objective interview process, and implementing DEI principles into a program. Using PubMed and Google Scholar, we performed a non-systematic literature search of articles from January 2014 to January 2024. Search terms included combinations of "diversity", "equity", "inclusion", "residency", "holistic review", "applications", "interviews", and "initiatives". Additional resources were identified through citations of selected articles. Based on findings from these articles, Task Force members made recommendations for best practices. RESULTS: The diversity of practicing urologists is disproportionate to that of the United States population. Emerging evidence demonstrates that DEI efforts in healthcare are associated with better outcomes and reduction in healthcare inequities. We offer strategies for residency programs to integrate DEI initiatives into their recruitment, application review, and interview process. Furthermore, we address extending DEI principles into a program's mission and culture to create an inclusive environment conducive to training and supporting individuals from unique backgrounds. CONCLUSION: It is critical to recruit and retain diverse talent in urology to improve patient care. We urge residency programs and their supporting institutions to adopt DEI principles into their recruitment efforts.

Neuroprotective effects of umbelliferone and esculetin in a mouse model of Parkinson's disease.

The production of reactive oxygen species and mitochondrial dysfunction in the brain are both associated with the progression of several neurodegenerative diseases, including Parkinson's disease. These characteristics are also observed when rodents are exposed to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a compound that causes nigrostriatal dopaminergic neurotoxicity and that has been used previously for assessing the effectiveness of neuroprotective agents. In this study, the neuroprotective effects of two coumarins, umbelliferone and esculetin, against MPTP-induced neurotoxicity were examined in C57BL/6J mice. The results show that dietary administration of umbelliferone and esculetin significantly attenuated MPTP-induced neurotoxicity in the substantia nigra pars compacta but not striatum, as measured by tyrosine hydroxylase staining. Both coumarins also prevented an MPTP-induced increase in nitrosative stress as measured by 3-nitrotyrosine immunoreactivity and also maintained glutathione levels in MPTP-exposed mice as well as in cell lines exposed to the metabolite 1-methyl-4-phenylpyridinium. Umbelliferone and esculetin also prevented MPTP-dependent caspase 3 activation, an indicator of apoptosis, but did not inhibit monoamine oxidase activity. This is the first time that the neuroprotective capabilities of these coumarins have been demonstrated, and the results indicate that umbelliferone and esculetin can protect against MPTP-induced neurotoxicity in the mouse. These compounds can cross the blood-brain barrier, so their effectiveness indicates that they have the potential to protect in neurodegenerative disease such as Parkinson's disease.

Decoupled roles for the atypical, bifurcated binding pocket of the ybfF hydrolase.

Serine hydrolases have diverse intracellular substrates, biological functions, and structural plasticity, and are thus important for biocatalyst design. Amongst serine hydrolases, the recently described ybfF enzyme family are promising novel biocatalysts with an unusual bifurcated substrate-binding cleft and the ability to recognize commercially relevant substrates. We characterized in detail the substrate selectivity of a novel ybfF enzyme from Vibrio cholerae (Vc-ybfF) by using a 21-member library of fluorogenic ester substrates. We assigned the roles of the two substrate-binding clefts in controlling the substrate selectivity and folded stability of Vc-ybfF by comprehensive substitution analysis. The overall substrate preference of Vc-ybfF was for short polar chains, but it retained significant activity with a range of cyclic and extended esters. This broad substrate specificity combined with the substitutional analysis demonstrates that the larger binding cleft controls the substrate specificity of Vc-ybfF. Key selectivity residues (Tyr116, Arg120, Tyr209) are also located at the larger binding pocket and control the substrate specificity profile. In the structure of ybfF the narrower binding cleft contains water molecules prepositioned for hydrolysis, but based on substitution this cleft showed only minimal contribution to catalysis. Instead, the residues surrounding the narrow binding cleft and at the entrance to the binding pocket contributed significantly to the folded stability of Vc-ybfF. The relative contributions of each cleft of the binding pocket to the catalytic activity and folded stability of Vc-ybfF provide a valuable map for designing future biocatalysts based on the ybfF scaffold.

The NF-κB subunit c-Rel stimulates cardiac hypertrophy and fibrosis.

Cardiac remodeling and hypertrophy are the pathological consequences of cardiovascular disease and are correlated with its associated mortality. Activity of the transcription factor NF-κB is increased in the diseased heart; however, our present understanding of how the individual subunits contribute to cardiovascular disease is limited. We assign a new role for the c-Rel subunit as a stimulator of cardiac hypertrophy and fibrosis. We discovered that c-Rel-deficient mice have smaller hearts at birth, as well as during adulthood, and are protected from developing cardiac hypertrophy and fibrosis after chronic angiotensin infusion. Results of both gene expression and cross-linked chromatin immunoprecipitation assay analyses identified transcriptional activators of hypertrophy, myocyte enhancer family, Gata4, and Tbx proteins as Rel gene targets. We suggest that the p50 subunit could limit the prohypertrophic actions of c-Rel in the normal heart, because p50 overexpression in H9c2 cells repressed c-Rel levels and the absence of cardiac p50 was associated with increases in both c-Rel levels and cardiac hypertrophy. We report for the first time that c-Rel is highly expressed and confined to the nuclei of diseased adult human hearts but is restricted to the cytoplasm of normal cardiac tissues. We conclude that c-Rel-dependent signaling is critical for both cardiac remodeling and hypertrophy. Targeting its activities could offer a novel therapeutic strategy to limit the effects of cardiac disease.

Occupational exposure and mortality among workers at three titanium dioxide plants.

BACKGROUND: A cohort of 3,607 workers employed in three DuPont titanium dioxide production facilities was followed from 1935 through 2006. METHODS: Combined and plant-specific cohort mortality was compared with the overall US population and other DuPont employees. The relationships between selected causes of death and annual cumulative exposures to titanium dioxide and chloride were investigated using Poisson regression methods to examine trends with increasing exposure. RESULTS: Among the 833 deaths, no causes of deaths were statistically significantly elevated either overall or plant-specific when compared to the US population. Compared to DuPont workers, statistically significantly elevated SMRs for all causes, all cancers, and lung cancers were found driven by the workers at the oldest plant. Comparing increasing exposure groups to the lowest group, disease risk did not increase with exposure. CONCLUSIONS: There was no indication of a positive association between occupational exposure and death from all causes, all cancers, lung cancers, non-malignant respiratory disease, or all heart disease.

Large-scale activation likelihood estimation meta-analysis of parkinsonian disorders.

Parkinsonism is a feature of several neurodegenerative disorders, including Parkinson's disease, progressive supranuclear palsy, corticobasal syndrome and multiple system atrophy. Neuroimaging studies have yielded insights into parkinsonian disorders; however, due to variability in results, the brain regions consistently implicated in these disorders remain to be characterized. The aim of this meta-analysis was to identify consistent brain abnormalities in individual parkinsonian disorders (Parkinson's disease, progressive supranuclear palsy, corticobasal syndrome and multiple system atrophy) and to investigate any shared abnormalities across disorders. A total of 44 591 studies were systematically screened following searches of two databases. A series of whole-brain activation likelihood estimation meta-analyses were performed on 132 neuroimaging studies (69 Parkinson's disease; 23 progressive supranuclear palsy; 17 corticobasal syndrome; and 23 multiple system atrophy) utilizing anatomical MRI, perfusion or metabolism PET and single-photon emission computed tomography. Meta-analyses were performed in each parkinsonian disorder within each imaging modality, as well as across all included disorders. Results in progressive supranuclear palsy and multiple system atrophy aligned with current imaging markers for diagnosis, encompassing the midbrain, and brainstem and putamen, respectively. PET imaging studies of patients with Parkinson's disease most consistently reported abnormality of the middle temporal gyrus. No significant clusters were identified in corticobasal syndrome. When examining abnormalities shared across all four disorders, the caudate was consistently reported in MRI studies, whilst the thalamus, inferior frontal gyrus and middle temporal gyri were commonly implicated by PET. To our knowledge, this is the largest meta-analysis of neuroimaging studies in parkinsonian disorders and the first to characterize brain regions implicated across parkinsonian disorders.

Mapping Essential Tremor to a Common Brain Network Using Functional Connectivity Analysis.

BACKGROUND AND OBJECTIVES: The cerebello-thalamo-cortical circuit plays a critical role in essential tremor (ET). However, abnormalities have been reported in multiple brain regions outside this circuit, leading to inconsistent characterization of ET pathophysiology. Here, we test whether these mixed findings in ET localize to a common functional network and whether this network has therapeutic relevance. METHODS: We conducted a systematic literature search to identify studies reporting structural or metabolic brain abnormalities in ET. We then used 'coordinate network mapping,' which leverages a normative connectome (n = 1,000) of resting-state fMRI data to identify regions commonly connected to findings across all studies. To assess whether these regions may be relevant for the treatment of ET, we compared our network with a therapeutic network derived from lesions that relieved ET. Finally, we investigated whether the functional connectivity of this ET symptom network is abnormal in an independent cohort of patients with ET as compared with healthy controls. RESULTS: Structural and metabolic brain abnormalities in ET were located in heterogeneous regions throughout the brain. However, these coordinates were connected to a common functional brain network, including the cerebellum, thalamus, motor cortex, precuneus, inferior parietal lobe, and insula. The cerebellum was identified as the hub of this network because it was the only brain region that was both functionally connected to the findings of over 90% of studies and significantly different in connectivity compared with a control data set of other movement disorders. This network was strikingly similar to the therapeutic network derived from lesions improving ET, with key regions aligning in the thalamus and cerebellum. Furthermore, positive functional connectivity between the cerebellar network hub and the sensorimotor cortices was significantly reduced in patients with ET compared with healthy controls, and connectivity within this network was correlated with tremor severity and cognitive functioning. DISCUSSION: These findings suggest that the cerebellum is the central hub of a network commonly connected to structural and metabolic abnormalities in ET. This network may have therapeutic utility in refining and informing new targets for neuromodulation of ET.

Mapping a network for tics in Tourette syndrome using causal lesions and structural alterations.

Tics are sudden stereotyped movements or vocalizations. Cases of lesion-induced tics are invaluable, allowing for causal links between symptoms and brain structures. While a lesion network for tics has recently been identified, the degree to which this network translates to Tourette syndrome has not been fully elucidated. This is important given that patients with Tourette syndrome make up a large portion of tic cases; therefore, existing and future treatments should apply to these patients. The aim of this study was to first localize a causal network for tics from lesion-induced cases and then refine and validate this network in patients with Tourette syndrome. We independently performed 'lesion network mapping' using a large normative functional connectome (n = 1000) to isolate a brain network commonly connected to lesions causing tics (n = 19) identified through a systematic search. The specificity of this network to tics was assessed through comparison to lesions causing other movement disorders. Using structural brain coordinates from prior neuroimaging studies (n = 7), we then derived a neural network for Tourette syndrome. This was done using standard anatomical likelihood estimation meta-analysis and a novel method termed 'coordinate network mapping', which uses the same coordinates, yet maps their connectivity using the aforementioned functional connectome. Conjunction analysis was used to refine the network for lesion-induced tics to Tourette syndrome by identifying regions common to both lesion and structural networks. We then tested whether connectivity from this common network is abnormal in a separate resting-state functional connectivity MRI data set from idiopathic Tourette syndrome patients (n = 21) and healthy controls (n = 25). Results showed that lesions causing tics were distributed throughout the brain; however, consistent with a recent study, these were part of a common network with predominant basal ganglia connectivity. Using conjunction analysis, coordinate network mapping findings refined the lesion network to the posterior putamen, caudate nucleus, globus pallidus externus (positive connectivity) and precuneus (negative connectivity). Functional connectivity from this positive network to frontal and cingulate regions was abnormal in patients with idiopathic Tourette syndrome. These findings identify a network derived from lesion-induced and idiopathic data, providing insight into the pathophysiology of tics in Tourette syndrome. Connectivity to our cortical cluster in the precuneus offers an exciting opportunity for non-invasive brain stimulation protocols.

Mortality among Tennessee Eastman Corporation (TEC) uranium processing workers, 1943-2019.

BACKGROUND: There are few occupational studies of women exposed to ionizing radiation. During World War II, the Tennessee Eastman Corporation (TEC) operated an electromagnetic field separation facility of 1152 calutrons to obtain enriched uranium (235U) used for the Hiroshima atomic bomb. Thousands of women were involved in these operations. MATERIALS AND METHODS: A new study was conducted of 13,951 women and 12,699 men employed at TEC between 1943 and 1947 for at least 90 days. Comprehensive dose reconstruction techniques were used to estimate lung doses from the inhalation of uranium dust based on airborne measurements. Vital status through 2018/2019 was obtained from the National Death Index, Social Security Death Index, Tennessee death records and online public record databases. Analyses included standardized mortality ratios (SMRs) and Cox proportional hazards models. RESULTS: Most workers were hourly (77.7%), white (95.6%), born before 1920 (58.3%), worked in dusty environments (57.0%), and had died (94.9%). Vital status was confirmed for 97.4% of the workers. Women were younger than men when first employed: mean ages 25.0 years and 33.0 years, respectively. The estimated mean absorbed dose to the lung was 32.7 mGy (max 1048 mGy) for women and 18.9 mGy (max 501 mGy) for men. The mean dose to thoracic lymph nodes (TLNs) was 127 mGy. Statistically significant SMRs were observed for lung cancer (SMR 1.25; 95% CI 1.19, 1.31; n = 1654), nonmalignant respiratory diseases (NMRDs) (1.23; 95% CI 1.19, 1.28; n = 2585), and cerebrovascular disease (CeVD) (1.13; 95% CI 1.08, 1.18; n = 1945). For lung cancer, the excess relative rate (ERR) at 100 mGy (95% CI) was 0.01 (-0.10, 0.12; n = 652) among women, and -0.15 (-0.38, 0.07; n = 1002) among men based on a preferred model for men with lung doses <300 mGy. NMRD and non-Hodgkin lymphoma were not associated with estimated absorbed dose to the lung or TLN. CONCLUSIONS: There was little evidence that radiation increased the risk of lung cancer, suggesting that inhalation of uranium dust and the associated high-LET alpha particle exposure to lung tissue experienced over a few years is less effective in causing lung cancer than other types of exposures. There was no statistically significant difference in the lung cancer risk estimates between men and women. The elevation of certain causes of death such as CeVD is unexplained and will require additional scrutiny of workplace or lifestyle factors given that radiation is an unlikely contributor since only the lung and lymph nodes received appreciable dose.

Do Skills Naturally Transfer Between Multiport and Single-Port Robotic Platforms? A Comparative Study in a Simulated Environment.

Introduction and Objective: With introduction of the da Vinci single-port (SP) system, we evaluated which multiport (MP) robotic skills are naturally transferable to the SP platform. Methods: Three groups of urologists: Group 1 (5 inexperienced in MP and SP), Group 2 (5 experienced in MP without SP experience), and Group 3 (2 experienced in both MP and SP) were recruited to complete a validated urethrovesical anastomosis simulation using MP followed by SP robots. Performance was graded using both GEARS and RACE scales. Subjective cognitive load measurements (Surg-TLX and difficulty ratings [/20] of instrument collisions camera and EndoWrist movement) were collected. Results: GEARS and RACE scores for Groups 1 and 3 were maintained on switching from MP to SP (Group 3 scored significantly higher on both systems). Surg-TLX and difficulty scores were also maintained for both groups on switching from MP and SP except for a significant increase in SP camera movement (+7.2, p = 0.03) in Group 1 compared to Group 3 that maintained low scores on both. Group 2 demonstrated significant lower GEARS (-2.9, p = 0.047) and RACE (-5.1, p = 0.011) scores on SP vs MP. On subanalysis, GEARS subscores for force sensitivity and robotic control (-0.7, p = 0.04; -0.9, p = 0.02) and RACE subscores for needle entry, needle driving, and tissue approximation (-0.9, p = 0.01; -1.0, p = 0.02; -1.0, p < 0.01) significantly decreased. GEARS (depth perception, bimanual dexterity, and efficiency) and RACE subscores (needle positioning and suture placement) were maintained. All participants scored significantly lower in knot tying on the SP robot (-1.0, p = 0.03; -1.2, p = 0.02, respectively). Group 2 reported higher Surg-TLX (+13 pts, p = 0.015) and difficulty ratings on SP vs MP (+11.8, p < 0.01; +13.6, p < 0.01; +14 pts, p < 0.01). Conclusions: The partial skill transference across robots raises the question regarding SP-specific training for urologists proficient in MP. Novices maintained difficulty scores and cognitive load across platforms, suggesting that concurrent SP and MP training may be preferred.