Conformation-Dependent Hydrogen-Bonding Interactions in a Switchable Artificial Metalloprotein.

Hydrogen-bonding (H-bonding) interactions in metalloprotein active sites can critically regulate enzyme function. Changes in the protein structure triggered by interplay with substrates, products, and partner proteins are often translated to the metallocofactor by way of specific changes in H-bond networks connected to the active site. However, the complexities of metalloprotein architecture and mechanism often preclude our ability to define the precise molecular interactions giving rise to these intricate regulatory pathways. To address this shortcoming, we have developed conformationally switchable artificial metalloproteins (swArMs) in which allosteric Gln-binding triggers protein conformational changes that impact the microenvironment surrounding an installed metallocofactor. Herein, we report a combined structural, spectroscopic, and computational approach to enhance the conformation-dependent changes in H-bond interactions surrounding the metallocofactor site of a swArM. Structure-informed molecular dynamics simulations were employed to predict point mutations that could enhance active site H-bond interactions preferentially in the Gln-bound holo-conformation of the swArM. Testing our predictions via the unique infrared spectral signals associated with the metallocofactor site, we have identified three key residues capable of imparting conformational control over the metallocofactor microenvironment. The resultant swArMs not only model biologically relevant structural regulation but also provide an enhanced Gln-responsive biological probe to be leveraged in future biosensing applications.

Evaluation of Asymmetries in Speech-in Noise Abilities in Audiologic Screening for Vestibular Schwannoma.

OBJECTIVES: Measures of speech-in-noise, such as the QuickSIN, are increasingly common tests of speech perception in audiologic practice. However, the effect of vestibular schwannoma (VS) on speech-in-noise abilities is unclear. Here, we compare the predictive ability of interaural QuickSIN asymmetry for detecting VS against other measures of audiologic asymmetry. METHODS: A retrospective review of patients in our institution who received QuickSIN testing in addition to a regular audiologic battery between September 2015 and February 2019 was conducted. Records for patients with radiographically confirmed, unilateral, pretreatment VSs were identified. The remaining records excluding conductive pathologies were used as controls. The predictive abilities of various measures of audiologic asymmetry to detect VS were statistically compared. RESULTS: Our search yielded 73 unique VS patients and 2423 controls. Receiver operating characteristic curve analysis showed that QuickSIN asymmetry was more sensitive and specific than pure-tone average asymmetry and word-recognition-in-quiet asymmetry for detecting VS. Multiple logistic regression analysis revealed that QuickSIN asymmetry was more predictive of VS (odds ratio [OR] = 1.23, 95% confidence interval [CI] [1.10, 1.38], p < 0.001) than pure-tone average asymmetry (OR = 1.04, 95% CI [1.00, 1.07], p = 0.025) and word-recognition-in-quiet asymmetry (OR = 1.03, 95% CI [0.99, 1.06], p = 0.064). CONCLUSION: Between-ear asymmetries in the QuickSIN appear to be more efficient than traditional measures of audiologic asymmetry for identifying patients with VS. These results suggest that speech-in noise testing could be integrated into clinical practice without hindering the ability to identify retrocochlear pathology.

Loxhd1 Mutations Cause Mechanotransduction Defects in Cochlear Hair Cells.

Sound detection happens in the inner ear via the mechanical deflection of the hair bundle of cochlear hair cells. The hair bundle is an apical specialization consisting of actin-filled membrane protrusions (called stereocilia) connected by tip links (TLs) that transfer the deflection force to gate the mechanotransduction channels. Here, we identified the hearing loss-associated Loxhd1/DFNB77 gene as being required for the mechanotransduction process. LOXHD1 consists of 15 polycystin lipoxygenase α-toxin (PLAT) repeats, which in other proteins can bind lipids and proteins. LOXHD1 was distributed along the length of the stereocilia. Two LOXHD1 mouse models with mutations in the 10th PLAT repeat exhibited mechanotransduction defects (in both sexes). While mechanotransduction currents in mutant inner hair cells (IHCs) were similar to wild-type levels in the first postnatal week, they were severely affected by postnatal day 11. The onset of the mechanotransduction phenotype was consistent with the temporal progression of postnatal LOXHD1 expression/localization in the hair bundle. The mechanotransduction defect observed in Loxhd1-mutant IHCs was not accompanied by a morphologic defect of the hair bundle or a reduction in TL number. Using immunolocalization, we found that two proteins of the upper and lower TL protein complexes (Harmonin and LHFPL5) were maintained in the mutants, suggesting that the mechanotransduction machinery was present but not activatable. This work identified a novel LOXHD1-dependent step in hair bundle development that is critical for mechanotransduction in mature hair cells as well as for normal hearing function in mice and humans.SIGNIFICANCE STATEMENT Hair cells detect sound-induced forces via the hair bundle, which consists of membrane protrusions connected by tip links. The mechanotransduction machinery forms protein complexes at the tip-link ends. The current study showed that LOXHD1, a multirepeat protein responsible for hearing loss in humans and mice when mutated, was required for hair-cell mechanotransduction, but only after the first postnatal week. Using immunochemistry, we demonstrated that this defect was not caused by the mislocalization of the tip-link complex proteins Harmonin or LHFPL5, suggesting that the mechanotransduction protein complexes were maintained. This work identified a new step in hair bundle development, which is critical for both hair-cell mechanotransduction and hearing.

Engineering a Conformationally Switchable Artificial Metalloprotein.

Many naturally occurring metalloenzymes are gated by rate-limiting conformational changes, and there exists a critical interplay between macroscopic structural rearrangements of the protein and subatomic changes affecting the electronic structure of embedded metallocofactors. Despite this connection, most artificial metalloproteins (ArMs) are prepared in structurally rigid protein hosts. To better model the natural mechanisms of metalloprotein reactivity, we have developed conformationally switchable ArMs (swArMs) that undergo a large-scale structural rearrangement upon allosteric effector binding. The swArMs reported here contain a Co(dmgH)2(X) cofactor (dmgH = dimethylglyoxime and X = N3-, H3C-, and iPr-). We used UV-vis absorbance and energy-dispersive X-ray fluorescence spectroscopies, along with protein assays, and mass spectrometry to show that these metallocofactors are installed site-specifically and stoichiometrically via direct Co-S cysteine ligation within the Escherichia coli glutamine binding protein (GlnBP). Structural characterization by single-crystal X-ray diffraction unveils the precise positioning and microenvironment of the metallocofactor within the protein fold. Fluorescence, circular dichroism, and infrared spectroscopies, along with isothermal titration calorimetry, reveal that allosteric Gln binding drives a large-scale protein conformational change. In swArMs containing a Co(dmgH)2(CH3) cofactor, we show that the protein stabilizes the otherwise labile Co-S bond relative to the free complex. Kinetics studies performed as a function of temperature and pH reveal that the protein conformational change accelerates this bond dissociation in a pH-dependent fashion. We present swArMs as a robust platform for investigating the interplay between allostery and metallocofactor regulation.

Does work-family balance mediate the relationship between work-family conflicts and job satisfaction of academicians?

Extreme workloads and strict work schedules make an individual cut their time and energy from their family domain, which may create a conflict, and this situation is called Work-Family Conflict (W-FC). Besides this, Work Family Balance (WFB) and Job Satisfaction (JS) issues are significant for academics because they have to play two roles (Job and Family) at the same time. This paper's fundamental objective was to investigate the indirect effect (mediation) of WFB through both forms of W-FC and JS. Following the convenience sampling technique, 250 married academicians from different private universities were considered for the sample size. Analysis of Moment Structures (AMOS) and Statistical Package for the Social Sciences (SPSS) was used to complete the data analyses. The outcomes of this study showed that out of the two forms, only W to F has significant adverse effects on JS. Also, it was found that to some extent, WFB showed a partial mediating effect only between W to FC and JS, whereas there was no mediating effect through F to WC and JS. These findings will help both academicians and higher authorities of private universities in Bangladesh. The higher authorities and decision-makers of the private universities in Bangladesh can identify the sources of W-FCs and take the necessary steps to mitigate the level of W-FCs.

Knowledge of primary health care physicians regarding depression in elderly.

OBJECTIVE: To assess the knowledge of primary healthcare physicians regarding elderly depression, and to study the association of different variables with the knowledge score. METHODS: The cross-sectional study was conducted from March 1 to June 30, 2019, in 30 primary health care centres under the Al-Karkh Health Directorate, Baghdad, Iraq, and comprised all physicians present at the time. Data were collected using a self-administered questionnaire about the knowledge regarding depression in elderly patients aged >65 years along with risk factors, diagnosis, treatment and prevention. Data were analysed using SPSS 24. RESULTS: Among the 149 participants, 69(46.3%) were aged >40 years, 116(77.9%) were females, 97(65.1%) were family physicians, and 96(65%) had good score regarding overall knowledge. Family physicians, specialists and those aged >40 years had significantly better knowledge level (p<0.05). CONCLUSIONS: The physicians had a good knowledge about elderly depression.

Comparison of corneal biomechanical properties following penetrating keratoplasty and deep anterior lamellar keratoplasty for keratoconus.

IMPORTANCE: Keratoplasty is a surgical procedure to create a more regular optical surface following biomechanical weakening of the cornea in keratoconus. The ideal keratoplasty procedure should also restore corneal biomechanics to that of the healthy cornea. BACKGROUND: This study aimed to evaluate and compare the biomechanical properties of corneas following penetrating keratoplasty (PKP) and predescematic deep anterior lamellar keratoplasty (DALK) to those of healthy eyes. DESIGN: Prospective cross-sectional study. PARTICIPANTS: Two cohorts of post-keratoplasty eyes (42 eyes with PKP and 27 eyes with DALK) with each other, and with a cohort of 152 healthy eyes. METHODS: All eyes were examined by slit-lamp biomicroscopy, tomography, anterior segment-OCT and non-contact tonometry CorVis ST (CST). MAIN OUTCOME MEASURES: CST biomechanical parameters, maximum corneal deformation (MCD) and corneal energy dissipation were compared between keratoplasty techniques, and with healthy eyes. RESULTS: The mean age of participants with PKP and DALK were 35 ± 13.7 and 36.1 ± 12.6 years, respectively. None of the CST parameters were significantly different between PKP and DALK eyes. However, when compared to healthy corneas, numerous parameters were significantly different for both keratoplasty techniques. Of note, MCD was significantly higher in PKP compared to DALK and healthy corneas, after controlling for co-factors. CONCLUSIONS AND RELEVANCE: Neither type of keratoplasty technique utilized in keratoconus completely restored corneal biomechanical properties to that of healthy corneas. However, PKP resulted in a greater number of parameters significantly different to healthy corneas, compared to DALK.

Sleep surgery in syndromic and neurologically impaired children.

PURPOSE: To examine surgery performed for obstructive sleep apnea (OSA) in children with syndromic or neurologic comorbidities. MATERIAL AND METHODS: Medical records of 375 children with OSA were retrospectively reviewed, including 142 patients with trisomy 21, 105 with cerebral palsy, 53 with muscular dystrophy, 32 with spinal muscular atrophy, 18 with mucopolysaccharidoses, 14 with achondroplasia, and 11 with Prader-Willi. OUTCOME MEASURES: Apnea-hypopnea index (AHI), complications, length of postoperative stay, and endoscopic findings. RESULTS: 228 patients received 297 surgical interventions, with the remainder undergoing observation or positive pressure ventilation. Adenoidectomy was the most common procedure performed (92.1% of patients), followed by tonsillectomy (91.6%). Average AHI decreased following tonsillectomy, from 12.4 to 5.7 (p = 0.002). The most common DISE finding was the tongue base causing epiglottic retroflexion. Lingual tonsillectomy also resulted in an insignificant decrease in the AHI. CONCLUSIONS: Adenotonsillectomy, when there is hypertrophy, remains the mainstay of management of syndromic and neurologically-impaired children with OSA. However, additional interventions are often required, due to incomplete resolution of the OSA. DISE is valuable in identifying remaining sites of obstruction and guiding future management.

Ventilator-associated events in children: A review of literature.

BACKGROUND: The complexity and variation in ventilator associated pneumonia (VAP) definitions in paediatrics may pose threats to the reliable identification of VAP. The revision of the surveillance definition to ventilator-associated event (VAE) has been mandated in adult populations, to overcome these issues. However, the evidence for application of the definition is unknown in children. OBJECTIVES: To review the evidence on the application of the new VAE surveillance definition in paediatric population and examine the potential challenges in clinical practice. REVIEW METHODS: A systematic approach was used to locate and synthesise the relevant paediatric literature. Studies were appraised according to epidemiological appraisal instrument (EAI) and the grades of evidence in the National Health Medical Research Council (NHMRC) guidelines. RESULTS: Seven studies met the inclusion criteria. Quality of study methods was above 50% on the EAI. The overall grade of evidence was assessed as C (satisfactory). The incidence of VAE in children ranged from 1.1 to 20.9 per 1000 ventilator days as a result of variations in surveillance criteria across included studies. There is little agreement between the new VAE and PNU/VAP surveillance definition in the identification of VAP. Challenges in the application of VAE surveillance were related to; the difference in modes of ventilation used in children versus adults, inconclusive criteria tailored to paediatric samples and a lack of data that support for automatic data extraction applied in paediatric studies. CONCLUSION: This review demonstrated promising evidence using the new VAE surveillance definition to define the VAE in children, but the level of the evidence is low. Before the possibility of real implementation in clinical settings, challenges related to VAE paediatric specific criteria' and the value of automated data collection need to be considered.

Perceived Academic and Psychological Stress among Adolescents in United Arab Emirates: Role of gender, age, depression, and high expectation of parents.

INTRODUCTION: Academic learning is the most important source of stress among young students worldwide and appears to be quite severe in eastern countries. We aimed to examine the relationship between academic stress and depression among adolescents. METHODS: A cross-sectional study was conducted among adolescents in United Arab Emirates using the Perceived Stress Scale - 14 (PSS-14) and Educational Stress Scale (ESS) for Adolescents (English and Arabic versions). RESULTS: The overall PSS was high in 186 (20%) of the respondents, and moderate in 695 (76%). A multiple regression model of predictors of the PSS showed statistically significant correlations between the total PSS-14 scores and age (p<0.0004), gender (p<0.0001), and grade (p<0.001). A multiple regression model of the PSS-14 questionnaire as predictors of the ESSA revealed that Four variables on PSS-14 were statistically significant predictors of the ESSA: history of depression (p<0.0001), content with academic achievement (p<0.0001), high academic expectation of parents (p<0.003), and a believe capable of meeting parental expectations (p<0.0001). CONCLUSIONS: Adolescents with severe academic stress need to be identified early. We suggest that an interdisciplinary team in the schools including student advisors and counselors be developed to further address stressors. In addition, students should be taught different stress management techniques such as cognitive behavioral skills to improve their ability to cope with school demands. The identification of stressors may lead to strategies that might address the quality of teaching and mental health evaluation among adolescents.

A new imaging technique for assessment of the effectiveness of long pulse Nd:YAG 532 nm laser in treatment of facial port wine stain.

BACKGROUND: PWS is a vascular malformation presented at birth and associated with a psychological problem to the patients. Many types of laser systems were used to solve this problem. AIM OF THE STUDY: To assess the efficacy of long-pulsed Nd:YAG 532-nm laser in the treatment of port wine stain both clinically and by imaging technique. PATIENTS AND METHODS: This is an interventional therapeutic clinical study for the treatment of facial port-twine stain with long-pulsed, 532-nm, Nd:YAG laser. The treatment sessions were done every 4 weeks for 12 sessions and follow-up after 3 months of the last session. The assessment of the response was done before and at the end of follow-up period, both objectively (percent of improvement, photo comparison by using PSNR) and subjectively (patient satisfaction). RESULTS: Sixteen patients completed all sessions of the treatment. The improvement score for the PWS were failure = 0%, mild = 6.25%, moderate = 12.5%, good = 31.25%, and excellent = 50%. The values of PSNR for all the patients have been recorded and were fewer than 25 which means that the response for the treated lesions was very good. CONCLUSION: The long-pulsed Nd:YAG laser 532 nm is an effective and safe method of treatment of facial PWSs without significant residue. The PSNR was a new, simple, cheap and noninvasive method for assessment of the response of PWSs to laser therapy.

Caecal malakoplakia: a rare mimic of malignancy.

Malakoplakia is a rare granulomatous disease. Its aetiology is unclear but possible theories include infection with microorganisms (especially Escherichia coli), immunosuppression and impaired lysosomal function. It has been commonly documented to affect the genitourinary tract but can affect any organ, with the gastrointestinal system being the next most affected. We present a woman in her 70s, with a 2-week history of right-sided abdominal pain, 13 years following her renal transplant. She was admitted for treatment of an E. coli bacteraemia. CT scan had shown a caecal pole mass, highly suspicious for malignancy. It was surgically resected, and histology revealed findings of malakoplakia within the colon. Surgical intervention was combined with a prolonged course of antibiotics for successful treatment. We highlight the ability of malakoplakia to mimic malignancy and should be considered in the differentials in the context of an immunosuppressed patient with radiological findings of a colonic mass.

An AUA Workforce Report: Data From the AUA Census Regarding Workplace Experiences Based on Gender.

INTRODUCTION: The AUA Workforce Workgroup contributes workforce-related questions to the annual AUA Census to better understand factors impacting the urologic community. This study aims to highlight pertinent gender differences potentially impacting career satisfaction and identify areas in which intervention could improve gender discrepancies. We hypothesize significant differences between males and females exist regarding responses to gender-related AUA Census questions. METHODS: The 2016 to 2021 AUA Censuses were examined to collate gender-specific data between self-identified male and female urologists. Up until 2021, the words male and female were used to define gender. The language was changed in the 2022 Census. Answers to AUA Census questions on topics with potential gender differences were grouped into major categories of workplace treatment and job satisfaction. RESULTS: Females were more likely than males to report negative differential treatment in primary practices (66.3% vs 2.7%, P < .001), felt they had limitations in seeing certain patients due to their gender (25.9% vs 2.4%, P = .021), experience gender bias in their practice (39.3% vs 1.2%, P < .001), and experience conflict regarding work and personal responsibility (95.4% vs 75%, P < .001). Females felt more barriers to professional success (93% vs 75%, P < .001) and felt a lack of control over staffing decisions or scheduling to be the greatest barriers (46.2%, P < .001). In contrast, males felt lack of time (33.7%, P = .060) to be the most significant barrier. Females were less likely than males to report feeling satisfied or very satisfied with their work-life balance (39.9% vs 57.7%, P < .001) and more likely to feel they do not have enough time for personal/family life (57.7% vs 33.6, P < .001). Females were also more likely than males to feel burnout (49.2% vs 35.3%, P < .001), which increased notably between 2016 and 2021. Females were also more likely to carry substantial education debt (18% vs 9%) and feel this contributed to burnout (38% vs 21.6%, P < .001). Notably, males and females demonstrated little difference in average worked hours (h) per week (mean 45.7 h for males, 43.7 h for females) and choosing medicine again as a career (88% males, 83.3% females; P= .143) and urology again as a specialty (93.3% males, 90.8% females; P = .307). CONCLUSIONS: Significant differences exist in career perceptions based on gender. Females report unique challenges in the workplace, and these factors contribute to less job satisfaction. Future work is needed to help characterize and address these differential workplace experiences.

The Role of Artificial Intelligence-Powered Imaging in Cerebrovascular Accident Detection.

Cerebrovascular accidents (CVAs) often occur suddenly and abruptly, leaving patients with long-lasting disabilities that place a huge emotional and economic burden on everyone involved. CVAs result when emboli or thrombi travel to the brain and impede blood flow; the subsequent lack of oxygen supply leads to ischemia and eventually tissue infarction. The most important factor determining the prognosis of CVA patients is time, specifically the time from the onset of disease to treatment. Artificial intelligence (AI)-assisted neuroimaging alleviates the time constraints of analysis faced using traditional diagnostic imaging modalities, thus shortening the time from diagnosis to treatment. Numerous recent studies support the increased accuracy and processing capabilities of AI-assisted imaging modalities. However, the learning curve is steep, and huge barriers still exist preventing a full-scale implementation of this technology. Thus, the potential for AI to revolutionize medicine and healthcare delivery demands attention. This paper aims to elucidate the progress of AI-powered imaging in CVA diagnosis while considering traditional imaging techniques and suggesting methods to overcome adoption barriers in the hope that AI-assisted neuroimaging will be considered normal practice in the near future. There are multiple modalities for AI neuroimaging, all of which require collecting sufficient data to establish inclusive, accurate, and uniform detection platforms. Future efforts must focus on developing methods for data harmonization and standardization. Furthermore, transparency in the explainability of these technologies needs to be established to facilitate trust between physicians and AI-powered technology. This necessitates considerable resources, both financial and expertise wise which are not available everywhere.

Synergistic Antibacterial Effect of ZnO Nanoparticles and Antibiotics against Multidrug-Resistant Biofilm Bacteria.

BACKGROUND: The misuse of antibiotics leads to a global increase in antibiotic resistance. Therefore, it is imperative to search for alternative compounds to conventional antibiotics. ZnO nanoparticles (Zn NP) are one of these alternatives because they are an effective option to overcome biofilm bacterial cells and a novel way to overcome multidrug resistance in bacteria. The current research study aims to characterize the efficacy of ZnO nanoparticles alone and in combination with other antibacterial drugs against bacterial biofilms. METHODS: ZnO NPs were prepared by co-precipitation method, and their anti-biofilm and antibacterial activities alone or combined with four types of broad-spectrum antibacterial (Norfloxacin, Colistin, Doxycycline, and Ampicillin) were evaluated against E. coli and S. aureus bacterial strains. Finally, the cytotoxicity and the hemolytic activity were evaluated. RESULTS: ZnO NPs were prepared, and results showed that their size was around 10 nm with a spherical shape and a zeta potential of -21.9. In addition, ZnO NPs were found to have a strong antibacterial effect against Gram-positive and Gram-negative microorganisms, with a minimum inhibitory concentration (MIC) of 62.5 and 125 µg/mL, respectively. Additionally, they could eradicate biofilmforming microorganisms at a concentration of 125 µg/m. ZnO NPs were found to be non-toxic to erythrocyte cells. Still, some toxicity was observed for Vero cells at effective concentration ranges needed to inhibit bacterial growth and eradicate biofilm-forming organisms. When combined with different antibacterial, ZnO NP demonstrated synergistic and additive effects with colistin, and the MIC and MBEC of the combination decreased significantly to 0.976 µg/mL against planktonic and biofilm strains of MDR Gram-positive bacteria, resulting in significantly reduced toxicity. CONCLUSION: The findings of this study encourage the development of alternative therapies with high efficacy and low toxicity. ZnO nanoparticles have demonstrated promising results in overcoming multi-drug resistant bacteria and biofilms, and their combination with colistin has shown a significant reduction in toxicity. Further studies are needed to investigate the potential of ZnO nanoparticles as a viable alternative to conventional antibiotics.

Patient satisfaction with topical ocular hypotensives.

BACKGROUND: The aim of this study is to assess patient satisfaction, convenience of use, ease of administration, side effects and treatment burden of topical ocular hypotensives. DESIGN: Prospective, observational cohort. PARTICIPANTS: Two thousand five hundred and forty-one patients with glaucoma or ocular hypertension. METHODS: The Treatment Impact Patient Satisfaction Scale (TIPSS) was administered by mail to all patients with glaucoma or ocular hypertension registered with Glaucoma New Zealand during a 3-month study period. The questionnaire assessed patient demographics; topical ocular hypotensive use including number of medications, frequency of administration, ease of use, class of medication, and presence/severity of side effects; impact on quality of life; and patient satisfaction. Univariate and multivariate analyses were performed to identify determinants of patient satisfaction. MAIN OUTCOME MEASURES: Patient satisfaction. RESULTS: Almost 80% of respondents were either 'very satisfied' or 'satisfied' with topical ocular hypotensives. Factors that were predictive of patient satisfaction included satisfaction with frequency of eye drop use {odds ratio (OR) 2.4 (95% confidence interval [CI] 1.8-3.1); P < 0.001}, subjective convenience (OR 2.6 [95% CI 2.0-3.4]; P < 0.001) and ease of administration (OR 2.5 [95% CI 2.0-3.3]; P < 0.001). Male gender was associated with lower satisfaction (OR 0.6 [95% CI 0.5-0.9]; P = 0.01). Factors that were not predictive of patient satisfaction included age, duration of eye drop use, class of medication and the presence of side effects. CONCLUSIONS: Patients with glaucoma and ocular hypotension are satisfied with topical ocular hypotensives. Efforts to improve patient satisfaction should focus on convenience and ease of administration.

Pharmacogenetic Effect of Thiopurine Methyl Transferase (TPMT) Gene Expression and Serum TNF on the Imuran Response in Ulcerative Colitis (UC) Iraqi Patients.

Background: Ulcerative colitis (UC), a chronic inflammatory bowel disease (IBD), exerts its impact on both rectal and colonic mucosa, with a growing incidence. This study aims to explore the pharmacogenetic influence of thiopurine methyl transferase (TPMT) gene expression and serum tumor necrosis factor (TNF) levels on the response to Imuran in Iraqi patients with UC. Methods: Seventy individuals with chronic UC and 30 healthy controls were enrolled in this investigation. RNA extraction using the triazole method and enzyme-linked immunosorbent assay (ELISA) for TNF measurement were employed. Patients, aged 15-50 years, underwent Imuran treatment. Results: Diverse responses to Imuran were observed among patients, with TPMT gene expression levels below 1 in 35 patients leading to side effects, while the remaining 35 patients exhibited positive responses with TPMT gene expression exceeding 1. Patients with varying degrees of severe, moderate, and mild UC associated with TNF showed a significant correlation with Imuran non-response. Conclusions: A distinct correlation was identified between TPMT gene expression and Imuran therapy outcomes in UC patients. Further investigation is warranted to elucidate the underlying mechanism, positioning the TPMT gene as a potential therapeutic target for mitigating the impact of UC.

Natural History of Cystic Vestibular Schwannomas.

OBJECTIVE: To determine the natural history of cystic vestibular schwannomas (VS). STUDY DESIGN: Retrospective cohort. SETTING: Single tertiary academic hospital. PATIENTS: Adults diagnosed with cystic VS who had at least 2 MRIs performed at least 6 months apart between 2008 and 2016 with no intervening treatment. MAIN OUTCOME MEASURES: Volumetric growth rates of both the entire tumor and individual cystic and solid components were measured. Linear growth rate of the entire tumor was assessed using the largest diameter parallel to the petrous face at the cerebellopontine angle (CPA). RESULTS: Twenty-one patients met inclusion criteria. The average volumetric growth rate of the tumor was 1.1 ± 2 (range: -1.2 to 7.8), while the average growth rate of the cystic component was 0.8 ± 1.6 (range: -0.5 to 5.3) cm3/year. The CPA diameter of the tumor demonstrated an average linear growth rate of was 1.2 ± 4.4 (range: -8to 13.5) mm/year. With regards to tumor diameter, 9/21 (42.9%) remained stable, 3/21 (14.2%) decreased in size, while 9/21 (42.9%) increased in size. CONCLUSIONS: Cystic tumors demonstrate a wide variability in growth rate. Larger, multi-center studies will be required to further compare this relationship to solid tumors.

The Effect of Oral Laxatives on Rectal Distension and Image Quality in Magnetic Resonance Imaging of the Prostate.

Introduction Increasing rectal size is associated with increased artefacts on magnetic resonance imaging (MRI) of the prostate and has the potential to degrade image quality. The objective of this study was to analyse the effect of oral laxative medication on rectal distension and image quality in prostate MRI. Methods Eighty patients prospectively received either 15 mg of oral senna (laxative group) or no medication (control group). Patients underwent prostate MRI according to standard local protocol and seven rectal dimensions on axial and sagittal images were measured. A subjective assessment of rectal distension was also made using a five-point Likert scale. Finally, artefacts on diffusion-weighted sequences were assessed using a four-point Likert scale. Results There was a small reduction in rectal diameter on sagittal images in the laxative group compared to the control group, with mean diameters of 27.1 mm and 30.0 mm respectively, p=0.02. There was no significant difference in rectal measurements of anteroposterior diameter, transverse diameter, or rectal circumference on axial imaging. Subjective scoring also demonstrated no significant difference in diffusion-weighted imaging quality between the laxative group and control group, p=0.82. Conclusion Bowel preparation with the oral laxative, senna, provided only a marginal decrease in rectal distension on one measure and no reduction in artefacts on diffusion-weighted sequences. The findings of this study do not support the routine use of this medication in patients undergoing prostate MRI.