Anterior approach sacrospinous hysteropexy: native tissue compared with mesh-augmented repair for primary uterovaginal prolapse management.

INTRODUCTION AND HYPOTHESIS: Anterior sacrospinous hysteropexy (SSH) was popularized by transvaginal mesh kits. Following mesh-kit market withdrawal, we hypothesized similar efficacy through native-tissue reattachment of the pubocervical fascia with fixation of the anterior cervix to the sacrospinous ligament. Few analyses for anterior native-tissue versus mesh-augmented SSH exist. METHODS: A retrospective analysis of women who underwent transvaginal anterior SSH between 01 January 2016 and 31 December 2022 was performed. Women who underwent a mesh-augmented (Uphold Lite Vaginal Support System™) versus native-tissue repair were compared. Composite success was defined as no bulge symptoms, no retreatment, and no recurrence beyond the hymen with apex nondescended > one third of the total vaginal length. Descriptive and bivariate statistics were obtained as indicated. RESULTS: Of 223 women screened, inclusion criteria were met by 124 (40 mesh-augmented; 84 native-tissue). There was no difference in pre-operative characteristics between groups. Composite success was demonstrated in 95.2% of women with a median follow-up of 224 days (range: 30-988). Two women in the mesh-augmented group reported bulge symptoms and underwent re-treatment with a pessary. Four women in the native-tissue group reported bulge symptoms; 3 underwent re-treatment (2 pessary, 1 surgery). There were no differences in composite success rates between groups (p=0.954). There were additionally no differences in intra-operative (p=0.752) or post-operative (p=0.292) complication rates between the groups. There were no mesh-related complications, including exposure or chronic pelvic pain. CONCLUSIONS: Ninety-five percent of women achieved surgical success and the use of mesh augmentation did not confer added benefit in terms of efficacy or complications when compared with native tissue. Further long-term data are needed to continue our assessment of native-tissue anterior SSH.

Examining potential mechanisms of testicular fibrosis in Klinefelter Syndrome: A review of current understanding.

BACKGROUND: Men with Klinefelter Syndrome develop some degree of seminiferous tubule degeneration, hyalinization, and fibrosis by adulthood. However, the pathophysiology surrounding testicular fibrosis in Klinefelter Syndrome patients remains incompletely understood. OBJECTIVES: To perform a systematic review of literature studying the mechanisms of fibrosis initiation or propagation in Klinefelter Syndrome testes. MATERIALS/METHODS: PubMed was searched systematically for articles specific to Klinefelter Syndrome and the process of fibrosis. Articles that did not contain original data or specifically addressed the target material were excluded. Additional references were extracted when pertinent from the reference lists of included studies. RESULTS: Primary search yielded 139 articles for abstract review, which was narrowed to 16 for full-text review. Following full-text review, eight contained original data and met topic criteria, with one paper added from reference review for a total of nine papers. DISCUSSION: The date range for included papers was 1992-2022. The proposed mechanisms of fibrosis mainly were centered around the impact of altered Sertoli cells on germ cells, the hormonal impact on Leydig cells, the inflammation mediated by mast cells, or the fibrous extracellular matrix deposition by peritubular myoid cells. Additionally, discussions of the role of the altered microvasculature and the specific proteins involved in the blood-testis barrier or the seminiferous tubule architecture are reviewed. Recent papers have incorporated advanced sequencing and offer future directions for targeted gene expression analysis. Still, much of the published data consists solely of immunohistological assessment by age range, creating difficulties in extrapolating causality. CONCLUSION: The specific initiating factors of fibrosis of the seminiferous tubules and the propagation mechanisms unique to Klinefelter Syndrome remain incompletely understood with a relative paucity of data. Nonetheless, academic interest is increasing in this field as it may further elucidate the pathophysiology behind Klinefelter syndrome.

Urine leaks in children sustaining blunt renal trauma.

BACKGROUND: Few consensus statements exist to guide the timely diagnosis and management of urine leaks in children sustaining blunt renal trauma (BRT). The aims of this study were to characterize kidney injuries among children who sustain BRT, evaluate risk factors for urine leaks, and describe the negative impact of urinoma on patient outcomes and resource consumption. METHODS: A retrospective review was performed of 347 patients, younger than 19 years, who presented with BRT to a single American College of Surgeons-verified Level I Pediatric Trauma Center between 2005 and 2020. Frequency of and risk factors for urine leak after BRT were evaluated, and impact on patient outcomes and resource utilization were analyzed. RESULTS: In total, 44 (12.7%) patients developed urine leaks, which exclusively presented among injury Grade 3 (n = 5; 11.4%), Grade 4 (n = 27; 61.4%), and Grade 5 (n = 12; 27.3%). A minority of urine leaks (n = 20; 45.5%) were discovered on presenting CT scan but all within 3 days. Kidney-specific operative procedures (nephrectomy, cystoscopy with J/ureteral stent, percutaneous nephrostomy) were more common among urine leak patients (n = 17; 38.6%) compared with patients without urine leaks (n = 3; 1.0%; p = 0.001). Patients with urine leak had more frequent febrile episodes during hospital stay (n = 24; 54.5%; p = 0.001) and showed increased overall 90-day readmission rates (n = 14; 33.3%; p < 0.001). Independent risk factors that associated with urine leak were higher grade (odds ratio [OR], 7.9; 95% confidence interval [CI], 2.6-24.3; p < 0.001), upper-lateral quadrant injuries (OR, 2.9; 95% CI, 1.2-7.1; p = 0.02), and isolated BRT (OR, 2.6; 95% CI, 1.0-6.5; p = 0.04). CONCLUSION: In a large cohort of children sustaining BRT, urine leaks result in considerable morbidity, including more febrile episodes, greater 90-day readmission rates, and increased operative or image-guided procedures. This study is the first to examine the relationship between kidney quadrant injury and urine leaks. Higher grade (Grade 4-5) injury, upper lateral quadrant location, and isolated BRT were independently predictive of urine leaks. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Cervical Sagittal Alignment in Patients with Cervical Spondylotic Myelopathy: An Observational Study From the Canadian Spine Outcomes and Research Network.

STUDY DESIGN: Prospective cohort study. OBJECTIVE: Among patients with CSM, we aimed to evaluate the extent to which: (1) Preoperative cervical sagittal alignment is associated with health-related quality of life, function, and symptoms; (2) Surgery leads to changes in cervical sagittal alignment; and (3) Postoperative cervical sagittal alignment is associated with health-related quality of life, function, and symptoms at 12 months of follow-up. SUMMARY OF BACKGROUND DATA: The importance of maintaining or improving cervical sagittal alignment in the surgical management of patients with CSM has not been established. METHODS: We measured C2-C7 Cobb angle, T1 slope, and C2-C7 cervical sagittal vertical axis (cSVA). We tested for associations with Neck Disability Index, Pain Scales for neck and arm pain, EuroQol 5D, Short Form 12 Physical and Mental Component Summaries, and modified Japanese Orthopaedic Association scores. We adjusted for potential confounders using multiple linear regression, and we performed various prespecified subgroup (cSVA > 40 mm, surgical approach) and sensitivity analyses. RESULTS: Among 250 patients, adjusted analyses yielded significant inverse associations prior to surgery between each of cSVA and T1 slope with SF12 Physical Component Summaries (T1 slope: -0.14, 95% CI -0.26 to -0.01, P = 0.03; C2-C7 cSVA: -0.13, 95% CI --0.21 to -0.05 P < 0.01). Surgery was associated with a small but statistically significant increase in cSVA across the cohort (+5.8 mm [SD 11.7], P < 0.01) but no change in Cobb angle or T1 slope. At 12-months after surgery, there were no significant associations between alignment parameters or change in alignment and any measures of health-related quality of life, function, or symptoms. Results were consistent across subgroup and sensitivity analyses. CONCLUSION: Increased cSVA and T1 slope were associated with inferior health-related quality of life at presentation among patients with CSM, but no significant associations were observed following surgical treatment.Level of Evidence: 3.

Are There Heterogeneous Impacts of Air Pollution on Mental Health?

Many studies reveal that air pollution is related to mental health. However, the level of impact and the regulatory mechanism of air pollution on different types of mental health are unknown. This paper examines the heterogeneous impact and mediating mechanisms of air pollution on mental health based on data of 51 countries from 2010 to 2017 by using panel Tobit random effect model, mediating effect model, and bootstrap test. The findings show that, firstly, there is heterogeneous impact of air pollution on different types of mental health. Specifically, air pollution has a significant positive impact on depression; and the impacts on happiness and anxiety are closely related to income level. Secondly, the heterogeneous impact of air pollution on mental health is contingent on income levels. Thirdly, the heterogeneous impacts under different income levels are exacerbated by different levels of education and population density. Lastly, the mediating effect of physical health on different types of mental health is also heterogeneous. To be specific, the effects of air pollution on depression and anxiety are partly mediated by physical health; whereas the effect on happiness is not. These findings contribute to the understanding of air pollution on public health, and have significant implication for social and public health policy makers.

Effects of cone versus multi-leaf collimation on dosimetry and neurotoxicity in patients with small arteriovenous malformations treated by stereotactic radiosurgery.

PURPOSE/OBJECTIVE: Linear accelerator (LINAC) based stereotactic radiosurgery (SRS) for arteriovenous malformations (AVMs) is delivered with cone or multileaf collimators (MLCs), and favorable dosimetry is associated with reduced radionecrosis in normal brain tissue. This study aims to determine whether cones or MLCs has better dosimetric characteristics, to predict differences in toxicity. METHODS: All patients treated for AVMs using LINAC SRS from 2003-2017 were examined retrospectively. Demographic data, volumes of normal tissue exposed to 12Gy (V12Gy[cc]) and 4Gy (V4Gy[cc]), maximal dose, and dose gradient were analyzed. Univariate and multivariate analyses were used to evaluate relationships between collimator type, dosimetric parameters, and toxicity. Propensity score matching was used to adjust for AVM size. RESULTS: Compared to MLC, cones were independently associated with reduced V12Gy[cc] after propensity score matching (p=0.008) and reduced neurotoxicity (p=0.016). Higher V12Gy[cc] (p=0.0008) and V4Gy[cc] (p=0.002) were associated with increased neurotoxicity. CONCLUSIONS: Treating AVMs with cone-based SRS over MLC-based SRS may improve dosimetry and reduce toxicities.

Stereotactic Radiosurgery and Hypofractionated Stereotactic Radiotherapy for Nonfunctioning Pituitary Adenoma.

Objectives Hypofractionated stereotactic radiotherapy (HSRT) in two to five fractions may offer patients with large nonfunctioning pituitary adenomas (NFPAs) with chiasm involvement a safe and effective treatment over a single week. However, little has been reported regarding this novel approach. Design We compared the feasibility, outcomes, and toxicity of single-fraction stereotactic radiosurgery and HSRT. Setting This study was conducted at a tertiary academic referral center. Participants After approval by the institutional review board, we performed a retrospective cohort study of patients treated at our institution with stereotactic radiosurgery (SRS) and HSRT for NFPA. Selection for SRS or HSRT was based on clinicopathologic factors including tumor size and cavernous sinus invasion at the discretion of the treating physician. Main Outcome Measures Local control, endocrinopathy, and radiation-associated toxicity were evaluated by binary logistic regression and Cox's proportional hazards regression. Results A total of 45 patients with mean follow-up of 5 years were enrolled including 26 patients treated by HSRT with mean follow-up of 3 years and 19 patients treated by SRS with median follow-up of 6 years. Clinicopathologic characteristics were balanced between cohorts. Local failure at last follow-up was 5% in the SRS cohort and 8% in the HSRT cohort, and rates of post-SRS endocrinopathy were similar between each cohort. Late complications including radionecrosis, visual deficit, and secondary malignancy were minimal in either cohort. Conclusions HSRT is an appropriate treatment strategy for patients with NFPAs, particularly for optic pathway preservation in the setting of large tumors with chiasm involvement. Further studies are needed to optimize fractionated approaches and patient selection.

Uncommon Bilateral Absence of Long Heads of the Biceps Tendons in Twin Sisters: A Report of 2 Cases.

We present 2 cases, 45-year-old identical twin sisters, with bilateral congenital absence of the long head of the biceps tendon (LHBT); 1 twin was symptomatic, while the other was not. Variations of the intra-articular portion of this tendon are widely reported, but there are few reports of cases with absent LHBT. These cases may be of particular interest to radiologists and surgeons because they demonstrate that absent biceps when congenital in nature may not always coincide with symptoms.

In silico screening identifies a novel small molecule inhibitor that counteracts PARP inhibitor resistance in ovarian cancer.

Poly ADP-ribose polymerase (PARP) inhibitors are promising targeted therapy for epithelial ovarian cancer (EOC) with BRCA mutations or defective homologous recombination (HR) repair. However, reversion of BRCA mutation and restoration of HR repair in EOC lead to PARP inhibitor resistance and reduced clinical efficacy of PARP inhibitors. We have previously shown that triapine, a small molecule inhibitor of ribonucleotide reductase (RNR), impaired HR repair and sensitized HR repair-proficient EOC to PARP inhibitors. In this study, we performed in silico screening of small molecule libraries to identify novel compounds that bind to the triapine-binding pocket on the R2 subunit of RNR and inhibit RNR in EOC cells. Following experimental validation of selected top-ranking in silico hits for inhibition of dNTP and DNA synthesis, we identified, DB4, a putative RNR pocket-binding inhibitor markedly abrogated HR repair and sensitized BRCA-wild-type EOC cells to the PARP inhibitor olaparib. Furthermore, we demonstrated that the combination of DB4 and olaparib deterred the progression of BRCA-wild type EOC xenografts and significantly prolonged the survival time of tumor-bearing mice. Herein we report the discovery of a putative small molecule inhibitor of RNR and HR repair for combination with PARP inhibitors to treat PARP inhibitor-resistant and HR repair-proficient EOC.

Changes in FXR1 expression after Chemotherapy for Rhabdomyosarcoma.

BACKGROUND: Rhabdomyosarcoma (RMS) arises from abnormal muscle development. We reported previously that Fragile-X-Related 1 (FXR1), essential to normal myogenesis, was highly expressed in RMS relative to other embryonal tumors. This current study explored FXR1 expression across RMS disease characteristics and treatment response. METHODS: RMS patients ≤18 years (1980-2019; n = 152) were categorized according to tumor histology, PAX/FOXO1 translocation, and vital status. FXR1 protein expression was compared before and after chemotherapy. Impact of FXR1 expression on relapse-free (RFS) and overall survival (OS) was analyzed. RESULTS: FXR1 was most intensely expressed in the cytosol of undifferentiated rhabdomyoblasts. At diagnosis, FXR1 expression was ubiquitous and strong across all disease characteristics and foremost associated with worse RFS in translocation-positive patients (p = 0.0411). Among embryonal and translocation-negative RMS, survivors showed a significantly greater decrease in FXR1 expression after chemotherapy (p < 0.001) compared to decedents (p = 0.8). In contrast, alveolar and translocation-positive RMS specimens showed insignificant changes in FXR1 expression across therapy. As expected, alveolar histology, translocation presence, stage, and clinical group associated with worse survival. CONCLUSIONS: FXR1 was expressed strongly across RMS specimens at diagnosis regardless of disease or patient characteristics, and particularly in undifferentiated cells. Reduction in FXR1 expression after chemotherapy associated with improved survival for embryonal and translocation-negative RMS patients.

Smartphone Compatible versus Conventional Ophthalmoscope: A Randomized Crossover Educational Trial.

Objective The aim of the study is to compare performance and ease-of-use (EOU) of optic disk assessment using a smartphone direct ophthalmoscope attachment (D-EYE) to the gold standard direct ophthalmoscope (DO). Design The type of study involved is prospective, randomized, crossover, and educational trial. Participants The participants involved were first year medical students inexperienced in ophthalmoscopy. Methods Optic disks of standardized and volunteer patients were examined using the D-EYE and a conventional DO. Optic disk identification, EOU ratings of the devices, self-reported confidence level in their examination with the devices, and estimation of vertical cup-to-disk ratio (VCDR) were compared. Analyses included Chi-square tests, independent samples t -tests, correlations, and multivariable linear regression. Results Forty-four medical students voluntarily participated in the study. Students using the DO required more attempts (3.57 vs. 2.69, p = 0.010) and time (197.00 vs. 168.02 seconds, p = 0.043) to match the patient's fundus to the correct photograph. Overall EOU between the devices (6.40 vs. 4.79, p < 0.001) and overall confidence in examination (5.65 vs. 4.49, p = 0.003) were greater when using the D-EYE. There were no statistically significant differences in accuracy of VCDR estimations between the two ophthalmoscopes. Conclusion Smartphone ophthalmoscopy could offer additional learning opportunities in medical education and may be considered in clinical practice by non-specialist physicians given its greater EOU and increased success in visualizing the optic disk.

Obesity is Associated with Longer Survival Independent of Sarcopenia and Myosteatosis in Metastatic and/or Castrate-Resistant Prostate Cancer.

PURPOSE: Obesity (body mass index 30 kg/m2 or greater) is associated with better overall survival in metastatic prostate cancer. Conversely, low muscle mass (sarcopenia) and low muscle radiodensity (myosteatosis) are associated with worse overall survival in many cancers. This study seeks to evaluate the relationship of sarcopenia, myosteatosis and obesity with overall survival in men with metastatic or castrate-resistant prostate cancer. MATERIALS AND METHODS: Retrospective analysis of men with metastatic or castrate-resistant prostate cancer and computerized tomography of abdomen/pelvis presenting to the Vanderbilt Comprehensive Prostate Cancer Clinic from 2012 to 2017 was performed. Demographic, pathological and survival data were described, with sarcopenia and myosteatosis determined from abdominal skeletal muscle area and skeletal muscle radiodensity, respectively. Kaplan-Meier curves and log-rank tests estimated the effect of body composition on survival. Multivariable Cox proportional hazard models were performed adjusting for age, Charlson comorbidity index, race and clinical stage. ANOVA was used to compare obese and nonobese men with and without sarcopenia or myosteatosis. RESULTS: Of 182 men accrued, 37.4% were obese, 53.3% sarcopenic and 59.3% myosteatotic. Over a median followup of 33.9 months, body mass index was associated with reduced mortality (HR 0.93, p=0.02), as was visceral adiposity (HR 0.99, p=0.003). Men with high body mass index without sarcopenia/myosteatosis lived significantly longer than men with high body mass index with sarcopenia/myosteatosis or normal body mass index men (F[3,91]=4.03, p=0.01). CONCLUSIONS: Both high body mass index and visceral adiposity in metastatic or castrate-resistant prostate cancer are associated with reduced mortality, independent of sarcopenia and myosteatosis. Therefore, routine clinical workup should include calculation of body mass index and measurement of waist circumference. Morphometric analysis of computerized tomography imaging can identify patients at risk for poor prognosis.

Supracondylar Fractures: A Retrospective Chart Review Comparing Infection Rate, Antibiotic Use, Surgical Time and Cost of Full Surgical Preparation and Draping vs "Semi-Sterile" Technique.

BACKGROUND: Semi-sterile and full preparation and draping techniques are commonly used in closed reduction percutaneous pinning (CRPP) of supracondylar fractures. Debate exists whether full preparation and draping is safer than semi-sterile technique in regards to infection risk and the utility of pre-operative antibiotics. This study is a comparison of infection rates, pre-operative antibiotic administration, cost and surgical time between techniques. METHODS: A retrospective chart review of 336 pediatric patients with supracondylar fractures repaired with CRPP at our institution was completed between January 2014 and April 2018, 168 per technique. Infection rates, pre-operative antibiotic administration, preparation-to-incision time and cost in semi-sterile draping versus full preparation and draping techniques were compared. RESULTS: Of the 336 patients, 1/168 (0.1%) in the full preparation and draping group developed an infection compared to 0/168 (0%) patients in the semi-sterile group. Pre-operative antibiotics (Cefazolin) were administered to 76/168 (23%) patients in the full preparation and draping group and 0/168 (0%) in the semi-sterile group. The infection found received pre-operative antibiotics. Mean preparation-to-incision time for the semi-sterile group was 2.4±2.0 minutes and the full preparation and draping group was 9.9 ±4.2 minutes (p <0.001). Surgical supply cost was $80.72 [CDN] and 108.24$ [CDN], respectively, for the semi-sterile and full preparation and draping groups. CONCLUSION: Risk of infection using a semi-sterile draping technique was safe and comparable to a full preparation and draping technique when used in CRPP of supracondylar fractures. The administration of pre-operative antibiotics does not appear to make a difference in infection rates. Semi-sterile operative technique is cost effective and has decreased preparation-to-incision time.

Investigating the reaction and substrate preference of indole-3-acetaldehyde dehydrogenase from the plant pathogen Pseudomonas syringae PtoDC3000.

Aldehyde dehydrogenases (ALDHs) catalyze the conversion of various aliphatic and aromatic aldehydes into corresponding carboxylic acids. Traditionally considered as housekeeping enzymes, new biochemical roles are being identified for members of ALDH family. Recent work showed that AldA from the plant pathogen Pseudomonas syringae strain PtoDC3000 (PtoDC3000) functions as an indole-3-acetaldehyde dehydrogenase for the synthesis of indole-3-acetic acid (IAA). IAA produced by AldA allows the pathogen to suppress salicylic acid-mediated defenses in the model plant Arabidopsis thaliana. Here we present a biochemical and structural analysis of the AldA indole-3-acetaldehyde dehydrogenase from PtoDC3000. Site-directed mutants targeting the catalytic residues Cys302 and Glu267 resulted in a loss of enzymatic activity. The X-ray crystal structure of the catalytically inactive AldA C302A mutant in complex with IAA and NAD+ showed the cofactor adopting a conformation that differs from the previously reported structure of AldA. These structures suggest that NAD+ undergoes a conformational change during the AldA reaction mechanism similar to that reported for human ALDH. Site-directed mutagenesis of the IAA binding site indicates that changes in the active site surface reduces AldA activity; however, substitution of Phe169 with a tryptophan altered the substrate selectivity of the mutant to prefer octanal. The present study highlights the inherent biochemical versatility of members of the ALDH enzyme superfamily in P. syringae.

Are There Heterogeneous Impacts of National Income on Mental Health?

Understanding heterogeneous impact and mechanisms between national income and mental health are crucial to develop prevention and intervention strategies. Based on panel data from 2007 to 2017, this study explores the heterogeneous impact of national income on different types of mental health. Then, it analyzes the heterogeneous impact among countries with different income levels. Furthermore, the heterogeneous moderating effects of national income on mental health mechanisms are elaborated and the findings reveal several key conclusions: firstly, national income exerts a heterogeneous impact on different types of mental health. Rising national income is conducive to increase people's happiness and reduce their prevalence of anxiety disorders, but it increases the prevalence of depression disorders. Secondly, national income has a heterogeneous impact on different types of mental health among countries with different income levels. Furthermore, the heterogeneous influence mechanism of national income on mental health is mainly reflected in different types of mental health. Unemployment, social support and freedom can moderate the relationship between national income and depression, while social support, positive affect and negative affect can moderate the relationship between national income and anxiety. Finally, based on the conclusions of quantitative analysis, some important policy recommendations are proposed for policy makers.

Conservative management of bladder endometriosis with acute renal failure.

Endometriosis involving the bladder is rare, but generally has a severe presentation with prominent lower urinary tract symptoms and can progress to renal failure. As endometriosis has a significant effect on quality of life and fertility, treatment plans must be centered on the patient's symptoms, expectations, and priorities. We present a case of a 37-year-old African American female with advanced bladder endometriosis and consequent renal failure, who desired to avoid extensive surgery and maintain her fertility. This case highlights the importance of shared decision making in balancing disease management with patient autonomy.

Outcomes of stereotactic radiosurgery and hypofractionated stereotactic radiotherapy for refractory Cushing's disease.

PURPOSE: Hypofractionated stereotactic radiotherapy (HSRT) for refractory Cushing's disease may offer a condensed treatment schedule for patients with large tumors abutting the optic chiasm unsuitable for stereotactic radiosurgery (SRS). To-date only four patients have been treated by HSRT in the published literature. We investigated the feasibility, toxicity, and efficacy of HSRT compared to SRS. METHODS: After approval, we retrospectively evaluated patients treated at our institution for refractory Cushing's disease with SRS or HSRT. Study outcomes included biochemical control, time to biochemical control, local control, and late complications. Binary logistic regression and Cox proportional hazards regression evaluated predictors of outcomes. RESULTS: Patients treated with SRS (n = 9) and HSRT (n = 9) were enrolled with median follow-up of 3.4 years. Clinicopathologic details were balanced between the cohorts. Local control was 100% in both cohorts. Time to biochemical control was 6.6. and 9.5 months in the SRS and HSRT cohorts, respectively (p = 0.6258). Two patients in each cohort required salvage bilateral adrenalectomy. Late complications including secondary malignancy, radionecrosis, cranial nerve neuropathy, and optic pathway injury were minimal for either cohort. CONCLUSIONS: HSRT is an appropriate treatment approach for refractory Cushing's disease, particularly for patients with large tumors abutting the optic apparatus. Prospective studies are needed to validate these findings and identify factors suggesting optimal fractionation approaches.

Does the Credit Cycle Have an Impact on Happiness?

The 2008 international financial crisis triggered a heated discussion of the relationship between public health and the economic environment. We test the relationship between the credit cycle and happiness using the fixed effects model and explore the transmission channels between them by adding the moderating effect. The results show the following empirical regularities. First, the credit cycle has a negative correlation with happiness. This means that credit growth will reduce the overall happiness score in a country/region. Second, the transmission channels between the credit cycle and happiness are different during credit expansion and recession. Life expectancy and generosity can moderate the relationship between the credit cycle and happiness only during credit expansion. GDP per capita can moderate this relationship only during credit recession. Social support, freedom, and positive affect can moderate this relationship throughout the credit cycle. Third, the total impact of the credit cycle on happiness will become positive by the changes in the moderating effects. In general, we can improve subjective well-being if one of the following five conditions holds: (1) with the adequate support from the family and society, (2) with enough freedom, (3) with social generosity, (4) with a positive and optimistic outlook, and (5) with a high level of GDP per capita.

Novel taste test for nasolacrimal duct obstruction using denatonium benzoate: a randomized controlled pilot study.

OBJECTIVE: To evaluate a novel, simple, noninvasive method (known as the "bitter taste test") of establishing nasolacrimal duct patency in healthy asymptomatic eyes. DESIGN: Double-blind, randomized controlled pilot study. PARTICIPANTS: Healthy asymptomatic medical students, residents, and allied health staff at our institution. METHODS: Participants, aged 18-35 years (n = 28) with assumed normal lacrimal function, were randomized to the interventional group (100 parts per million denatonium benzoate in sterile water, n = 14) or to the control group (sterile water only, n = 14). All participants were pretreated with topical tetracaine in their right conjunctival cul-de sac, followed by 3 drops of the experimental solution spaced 1 minute apart. The primary outcome was whether participants reported a strong, persistent bitter taste. The secondary outcome was the time-to-taste. All participants received lacrimal irrigation. The Fisher's exact test was done using GraphPad online software. RESULTS: All participants in the interventional group reported the presence of the bitter solution. None of the participants in the control group reported bitterness (p < 0.001, Fisher's exact test). Time-to-taste was within 15 minutes for 71% of the intervention group (n = 10); within 30 minutes for 79% (n = 11); and within 2 hours for 100% (n = 14). The bitterness typically persisted for 1-2 hours. All participants had normal lacrimal systems to irrigation. No adverse events were reported. CONCLUSIONS: The bitter taste test demonstrates a promising ability to assess nasolacrimal duct patency under physiologic conditions in healthy participants. Further research is needed to validate this method in a clinical sample of patients with nasolacrimal duct obstruction.