Genome wide-scale CRISPR-Cas9 knockout screens identify a fitness score for optimized risk stratification in colorectal cancer.

BACKGROUND: The molecular complexity of colorectal cancer poses a significant challenge to the clinical implementation of accurate risk stratification. There is still an urgent need to find better biomarkers to enhance established risk stratification and guide risk-adapted treatment decisions. METHODS: we systematically analyzed cancer dependencies of 17 colorectal cancer cells and 513 other cancer cells based on genome-scale CRISPR-Cas9 knockout screens to identify colorectal cancer-specific fitness genes. A regression model was built using colorectal cancer-specific fitness genes, which was validated in other three independent cohorts. 30 published gene expression signatures were also retrieved. FINDINGS: We defined a total of 1828 genes that were colorectal cancer-specific fitness genes and identified a 22 colorectal cancer-specific fitness gene (CFG22) score. A high CFG22 score represented unfavorable recurrence and mortality rates, which was validated in three independent cohorts. Combined with age, and TNM stage, the CFG22 model can provide guidance for the prognosis of colorectal cancer patients. Analysis of genomic abnormalities and infiltrating immune cells in the CFG22 risk stratification revealed molecular pathological difference between the subgroups. Besides, drug analysis found that CFG22 high patients were more sensitive to clofibrate. INTERPRETATION: The CFG22 model provided a powerful auxiliary prediction tool for identifying colorectal cancer patients with high recurrence risk and poor prognosis, optimizing precise treatment and improving clinical efficacy.

Comparative immune profiling of pancreatic ductal adenocarcinoma progression among South African patients.

BACKGROUND: Pancreatic Ductal Adenocarcinoma (PDAC) is an aggressive cancer characterized by an immunosuppressive microenvironment. Patients from specific ethnicities and population groups have poorer prognoses than others. Therefore, a better understanding of the immune landscape in such groups is necessary for disease elucidation, predicting patient outcomes and therapeutic targeting. This study investigated the expression of circulating key immune cell markers in South African PDAC patients of African ancestry. METHODS: Blood samples were obtained from a total of 6 healthy volunteers (HC), 6 Chronic Pancreatitis (CP) and 34 PDAC patients consisting of 22 resectable (RPC), 8 locally advanced (LAPC) and 4 metastatic (MPC). Real-time Quantitative Polymerase Chain reactions (RT-qPCR), Metabolomics, Enzyme-Linked Immunosorbent Assay (ELISA), Reactive Oxygen Species (ROS), and Immunophenotyping assays were conducted. Statistical analysis was conducted in R (v 4.3.2). Additional analysis of single-cell RNA data from 20 patients (16 PDAC and 4 controls) was conducted to interrogate the distribution of T-cell and Natural Killer cell populations. RESULTS: Granulocyte and neutrophil levels were significantly elevated while lymphocytes decreased with PDAC severity. The total percentages of CD3 T-cell subpopulations (helper and double negative T-cells) decreased when compared to HC. Although both NK (p = 0.014) and NKT (p < 0.001) cell levels increased as the disease progressed, their subsets: NK CD56dimCD16- (p = 0.024) and NKTs CD56+ (p = 0.008) cell levels reduced significantly. Of note is the negative association of NK CD56dimCD16- (p < 0.001) cell levels with survival time. The gene expression analyses showed no statistically significant correlation when comparing the PDAC groups with the controls. The inflammatory status of PDAC was assessed by ROS levels of serum which were elevated in CP (p = 0.025), (RPC (p = 0.003) and LAPC (p = 0.008)) while no significant change was observed in MPC, compared to the HC group. ROS was shown to be positively correlated with GlycA (R = 0.45, p = 0.0096). Single-cell analyses showed a significant difference in the ratio of NKT cells per total cell counts in LAPC (p < 0.001) and MPC (p < 0.001) groups compared with HC, confirming observations in our sample group. CONCLUSION: The expression of these immune cell markers observed in this pilot study provides insight into their potential roles in tumour progression in the patient group and suggests their potential utility in the development of immunotherapeutic strategies.

Lax Uterosacral Ligament and Urge Urinary Incontinence: MRI Findings in Symptomatic Patients Versus Healthy Volunteers.

INTRODUCTION AND HYPOTHESIS: The objective was to explore the association between urge urinary incontinence (UUI) and lax uterosacral ligaments (USL) using MRI. METHODS: Sixty-seven female participants were recruited prospectively: 41 continent volunteers (control group) and 26 patients with UUI. Static proton density- and T2-weighted turbo spin echo sequences of MR images were used. A radiologist employed a standardized grid system to record structural observations of the USLs on sequentially numbered axial MR images and then applied a four-point grading scale to assess ligament visibility. MR images were interpreted by a radiologist and a urologist, and then validated by an expert radiologist. RESULTS: The comparison between the mean length of uterosacral ligaments in the control and UUI groups was highly statistically significant (p < 0.001). The mean length of the right USL was 38 ± 11 mm, and the left USL was 35 ± 12 mm in the UUI group. In the control group, the mean length of the USL was 22 ± 9 mm on the right side and 18 ± 9 mm on the left side, along their craniocaudal extent. The highest inter-observer agreement was on the level of origin and insertion (image numbers), whereas the lowest agreement was on the anatomical site of origin and insertion of the USL in both the control and UUI groups. CONCLUSIONS: The average length of USLs in patients with UUI is significantly longer than that in healthy continent women, indicating laxity. Our findings support the relationship between the laxity of the USL and UUI symptoms and have therapeutic implications.

Emergency Decompression of Orbital Emphysema, a Sight-Saving Tool in a Patient With Precious Eye.

A woman, 19 years old, with a history of falling from a height with resulting zygomatico-maxillar complex fracture on the right side, a mandibular fracture on the left side for which she underwent repair with plate insertion, and traumatic optic atrophy in her right eye, presented 9 months later with eye facial swelling, proptosis, and acute rapid loss of vision in the left eye. The diagnosis was done immediately aided by radiology assistance and a decision was taken to admit the patient to undergo urgent decompression to save the vision and the patient did recover well. This case presented here and the associated literature review focus on severe orbital emphysema with compressive optic neuropathy and orbital compartment syndrome as a morbidity that can exist with delayed presentation after trauma and not elicited by sneezing or forced blowing, as well as the drastic importance of brisk intervention, to save vision and prevent visual complications if left untreated.

The impact of incorporating dried cafeteria leftover food on growing APRI rabbits productivity, profitability and meat quality.

This study was conducted to investigate the effect of dried cafeteria leftover food (DCLF) incorporation in growing APRI rabbit diets on nutrient digestibility, live body weight, body weight gain, carcass traits, meat quality, blood parameters, and economic efficiency. Thirty-six APRI rabbits (6 weeks of age), after weaning, were randomly divided into three groups (12 rabbits/group, 613 ± 5 g). During the experiment, rabbits aged 6-14 weeks participated in the experiment. An approximate isocaloric and isonitrogenous composition was achieved in three pelleted experimental diets. For the rabbit groups D1 (as the control), D2, and D3, DCLF was added at doses of 0%, 17.5%, and 35%, respectively. Digestibility trails were carried out at the end of the feeding experiment to evaluate the nutritional and feeding values of the experimental diets. To examine the characteristics of the carcasses, the quality of the meat, the histopathological analysis, and the blood plasma parameters, three rabbits were slaughtered from each group. The results showed that the feeding values (TDN and DE), which had the greatest values, as well as the digesting coefficients for dry matter, organic matter, crude fiber, and ether extract between the D1 and D3 groups were significantly different (p < 0.05). On the contrary, the curde protein, nitrogen-free extract, and digestible crude protein of the examined diets showed no signifcant differences compared with the control diet. The level of DCLF incorporation in diets significantly (p < 0.05) increased the live body weight at 14 weeks; with D3 recording the highest values (2130.9 g) when compared to the D1 and D2 groups. A similar pattern was observed for both daily increase and total body gain (6-14 weeks). Feed conversion recorded insignificant differences among the experimental diets respecting the period 6-14 weeks of age. DCLF levels had a significant effect on dressing and giblet percentages. The chemical composition and color parameters of rabbit meat were similar (p > 0.05), except for fat%, which had the highest value in the D3 group (p < 0.05) compared to the D1 and D2 groups. Economic efficiency was improved by using DLCF up to 35% in terms of gross margin and feed cost/kg gain. In conclusion, using DCLF in the feeding system of rabbits could enhance productive performance, carcass traits, meat quality, and physiological function, as well as improve economic efficiency.

Environmental sustainability of post-orthodontic dental retainers: a comparative life-cycle assessment of Hawley and Essix retainers.

BACKGROUND: Environmental sustainability has been brought into the limelight due to the global climate crisis. This crisis is driven by human activities and even the healthcare sector is no exception. Within dentistry, orthodontics is a large global market; hence, the use of post-orthodontic retainers has a significant environmental footprint. The aim of this study was to determine the environmental sustainability of post-orthodontic retention using Hawley and Essix retainers. MATERIALS AND METHODS: A comparative life-cycle assessment (LCA) was carried out to compare the environmental impact of both retainers. All inputs and outputs were accounted for using the Ecoinvent database, v3.7.1, and openLCA software. Sixteen impact categories were used to determine their environmental burden. RESULTS: Of the 16 impact categories, the Hawley had a greater environmental burden than the Essix retainer in 12 categories. The Hawley's most significant contributors to its impact values are factory manufacturing and in-house production, with an average of 41.45% and 52.52%, respectively. For the Essix, the greatest contributor is factory manufacturing, with an average of 64.63%. However, when factoring in the lifespan of the retainers, the Essix would have a greater environmental impact than the Hawley retainer. LIMITATIONS: This study employed a comparative LCA. There were also assumptions made, but these were supported by research. CONCLUSIONS: On the basis of the evidence gathered in this study, Hawley retainers are more environmentally sustainable than Essix retainers. These results would better enable clinicians to factor in the environmental impact and make informed decisions on the choice of retainer type.

Approaches for Stereotactic Radiosurgery (SRS)/Stereotactic Radiotherapy (SRT) in brain metastases using different radiotherapy modalities (Feasibility study).

BACKGROUND: SRS and SRT are precise treatments for brain metastases, delivering high doses while minimizing doses to nearby organs. Modern linear accelerators enable the precise delivery of SRS/SRT using different modalities like three-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT), and Rapid Arc (RA). OBJECTIVE: This study aims to compare dosimetric differences and evaluate the effectiveness of 3DCRT, IMRT, and Rapid Arc techniques in SRS/SRT for brain metastases. METHODS: 10 patients with brain metastases, 3 patients assigned for SRT, and 7 patients for SRS. For each patient, 3 treatment plans were generated using the Eclipse treatment planning system using different treatment modalities. RESULTS: No statistically significant differences were observed among the three techniques in the homogeneity index (HI), maximum D2%, and minimum D98% doses for the target, with a p > 0.05. The RA demonstrated a better conformity index of 1.14±0.25 than both IMRT 1.21±0.26 and 3DCRT 1.37±0.31. 3DCRT and IMRT had lower Gradient Index values compared to RA, suggesting that they achieved a better dose gradient than RA. The mean treatment time decreased by 26.2% and 10.3% for 3DCRT and RA, respectively, compared to IMRT. In organs at risk, 3DCRT had lower maximum doses than IMRT and RA, but some differences were not statistically significant. However, in the brain stem and brain tissues, RA exhibited lower maximum doses compared to IMRT and 3DCRT. Additionally, RA and IMRT had lower V15Gy, V12Gy, and V9Gy values compared to 3DCRT. CONCLUSION: While 3D-CRT delivered lower doses to organs at risk, RA and IMRT provided better conformity and target coverage. RA effectively controlled the maximum dose and irradiated volume of normal brain tissue. Overall, these findings indicate that 3DCRT, RA, and IMRT are suitable for treating brain metastases in SRS/SRT due to their improved dose conformity and target coverage while minimizing dose to healthy tissues.

Effect of urea-treated rice straw, mixed with faba bean straw, on nutrient digestibility, blood metabolites and performance of growing lambs.

The present study aimed to use poor quality roughages, such as rice and faba bean straw, treated with or without urea, and their impacts on digestibility, rumen fermentation, some blood parameters, and growth performance of lambs. Twenty crossbred male lambs (1/4 Finland ×¾ Ossimi, 25±1.13kg live body weight) were chosen and divided into four groups. All lambs were fed rations of concentrated feed mixture at 2% of live weight with the following roughages ad libitum: URS (control group, untreated rice straw), TRS (urea-treated rice straw), FBS (faba bean straw), and TRS+FBS (mixture of TRS and FBS, 1:1). Nutrient digestibility and feeding values improved (P<0.05) with TRS+FBS lambs versus FBS, TRS and URS lambs. The highest numerical values of ruminal total volatile fatty acid (VFA) concentration in TRS lambs were recorded 23.9 ml.eq/dl followed by TRS+FBS, URS and FBS. Regarding to the ruminal parameters, there were no differences (P>0.05) among evaluated groups except for NH3-N, the highest concentration (P<0.05) was recorded in TRS lambs at 3 h post-feeding. Lambs of TRS, FBS and TRS+FBS showed faster growth (P<0.05) than those of the control (i.e., URS). Intakes of dry matter, total digestible nutrients, and digestible crude protein were numerically increased for TRS, FBS, and TRS+FBS. Feed conversion, as kg dry matter/kg gain, was improved for TRS, FBS, and TRS+FBS lambs versus URS. Daily gain of lambs increased (P<0.05) with lambs of TRS, FBS, and TRS+FBS but URS lambs showed a decrease (P<0.05) in daily gain. Feed conversion as kg dry matter intake/kg gain was improved (P<0.05) by feeding on TRS, FBS and TRS+FBS rations versus URS. The TRS+FBS lambs tended to have the highest economic efficiency versus URS, TRS and FBS lambs. It was concluded that urea-treated rice straw could be used as sole roughage or mixed with faba bean straw (1:1) in growing lambs' ration to improve their performance and economic efficiency without adversely affecting their health.The present study aimed to use poor quality roughages, such as rice and faba bean straw, treated with or without urea, and their impacts on digestibility, rumen fermentation, some blood parameters, and growth performance of lambs. Twenty crossbred male lambs (1/4 Finland ×¾ Ossimi, 25±1.13kg live body weight) were chosen and divided into four groups. All lambs were fed rations of concentrated feed mixture at 2% of live weight with the following roughages ad libitum: URS (control group, untreated rice straw), TRS (urea-treated rice straw), FBS (faba bean straw), and TRS+FBS (mixture of TRS and FBS, 1:1). Nutrient digestibility and feeding values improved (P<0.05) with TRS+FBS lambs versus FBS, TRS and URS lambs. The highest numerical values of ruminal total volatile fatty acid (VFA) concentration in TRS lambs were recorded 23.9 ml.eq/dl followed by TRS+FBS, URS and FBS. Regarding to the ruminal parameters, there were no differences (P>0.05) among evaluated groups except for NH3-N, the highest concentration (P<0.05) was recorded in TRS lambs at 3 h post-feeding. Lambs of TRS, FBS and TRS+FBS showed faster growth (P<0.05) than those of the control (i.e., URS). Intakes of dry matter, total digestible nutrients, and digestible crude protein were numerically increased for TRS, FBS, and TRS+FBS. Feed conversion, as kg dry matter/kg gain, was improved for TRS, FBS, and TRS+FBS lambs versus URS. Daily gain of lambs increased (P<0.05) with lambs of TRS, FBS, and TRS+FBS but URS lambs showed a decrease (P<0.05) in daily gain. Feed conversion as kg dry matter intake/kg gain was improved (P<0.05) by feeding on TRS, FBS and TRS+FBS rations versus URS. The TRS+FBS lambs tended to have the highest economic efficiency versus URS, TRS and FBS lambs. It was concluded that urea-treated rice straw could be used as sole roughage or mixed with faba bean straw (1:1) in growing lambs' ration to improve their performance and economic efficiency without adversely affecting their health.

Perinatal assessment of complex cesarean delivery: beyond placenta accreta spectrum.

Multiple cesarean deliveries are known to be associated with long-term postoperative consequences because of a permanent defect of the lower uterine segment wall and the development of thick pelvic adhesions. Patients with a history of multiple cesarean deliveries often present with large cesarean scar defects and are at heightened risk in subsequent pregnancies of cesarean scar ectopic pregnancy, uterine rupture, low-lying placenta or placenta previa, and placenta previa accreta. Moreover, large cesarean scar defects will lead to progressive dehiscence of the lower uterine segment with the inability to effectively reapproximate hysterotomy edge and repair at birth. Major remodeling of the lower uterine segment associated with true placenta accreta spectrum at birth, whereby the placenta becomes inseparable from the uterine wall, increases the rates of perinatal morbidity and mortality, especially when undiagnosed before delivery. Ultrasound imaging is currently not routinely used to evaluate the surgical risks of patients with a history of multiple cesarean deliveries, beyond the risk assessment of placenta accreta spectrum. Independent of accreta placentation, a placenta previa under a scarred, thinned partially disrupted lower uterine segment, covered by thick adhesions with the posterior wall of the bladder, poses a surgical risk and requires fine dissection and surgical expertise; however, data on the use of ultrasound to evaluate uterine remodeling and adhesions between the uterus and other pelvic organs are scarce. In particular, transvaginal sonography has been underused, including in patients with a high probability of placenta accreta spectrum at birth. Based on the best available knowledge, we discuss the role of ultrasound imaging in identifying the signs suggestive of major remodeling of the lower uterine segment and in mapping the changes in the uterine wall and pelvis, to enable the surgical team to prepare for all different types of complex cesarean deliveries. The need for postnatal confirmation of the prenatal ultrasound findings for all patients with a history of multiple cesarean deliveries, regardless of the diagnosis of placenta previa and placenta accreta spectrum, is discussed. We propose an ultrasound imaging protocol and a classification of the level of surgical difficulty at elective cesarean delivery to stimulate further research toward the validation of ultrasound signs by which these signs may be applied to improve surgical outcomes.

The role of transvaginal ultrasound in the third-trimester evaluation of patients at high risk of placenta accreta spectrum at birth.

BACKGROUND: Transvaginal ultrasound imaging has become an essential tool in the prenatal evaluation of the lower uterine segment and anatomy of the cervix, but there are only limited data on the role of transvaginal ultrasound in the management of patients at high risk of placenta accreta spectrum at birth. OBJECTIVE: This study aimed to evaluate the role of transvaginal sonography in the third trimester of pregnancy in predicting outcomes in patients with a high probability of placenta accreta spectrum at birth. STUDY DESIGN: This was a retrospective analysis of prospectively collected data of patients presenting with a singleton pregnancy and a history of at least 1 previous cesarean delivery and patients diagnosed prenatally with an anterior low-lying placenta or placenta previa delivered electively after 32 weeks of gestation. All patients had a least 1 detailed ultrasound examination, including transabdominal and transvaginal scans, within 2 weeks before delivery. Of note, 2 experienced operators, blinded to the clinical data, were asked to make a judgment on the likelihood of placenta accreta spectrum as a binary, low or high-probability of placenta accreta spectrum, and to predict the main surgical outcome (conservative vs peripartum hysterectomy). The diagnosis of accreta placentation was confirmed when one or more placental cotyledons could not be digitally separated from the uterine wall at delivery or during the gross examination of the hysterectomy or partial myometrial resection specimens. RESULTS: A total of 111 patients were included in the study. Abnormal placental tissue attachment was found in 76 patients (68.5%) at birth, and histologic examination confirmed superficial villous attachment (creta) and deep villous attachment (increta) in 11 and 65 cases, respectively. Of note, 72 patients (64.9%) had a peripartum hysterectomy, including 13 cases with no evidence of placenta accreta spectrum at birth because of failure to reconstruct the lower uterine segment and/or excessive bleeding. There was a significant difference in the distribution of placental location (X2=12.66; P=.002) between transabdominal and transvaginal ultrasound examinations, but both ultrasound techniques had similar likelihood scores in identifying accreta placentation that was confirmed at birth. On transabdominal scan, only a high lacuna score was significantly associated (P=.02) with an increased chance of hysterectomy, whereas on transvaginal scan, significant associations were found between the need for hysterectomy and the thickness of the distal part of the lower uterine segment (P=.003), changes in the cervix structure (P=.01), cervix increased vascularity (P=.001), and the presence of placental lacunae (P=.005). The odds ratio for peripartum hysterectomy were 5.01 (95% confidence interval, 1.25-20.1) for a very thin (<1-mm) distal lower uterine segment and 5.62 (95% confidence interval, 1.41-22.5) for a lacuna score of 3+. CONCLUSION: Transvaginal ultrasound examination contributes to both prenatal management and the prediction of surgical outcomes in patients with a history of previous cesarean delivery with and without ultrasound signs suggestive of placenta accreta spectrum. Transvaginal ultrasound examination of the lower uterine segment and cervix should be included in clinical protocols for the preoperative evaluation of patients at risk of complex cesarean delivery.

Impact of an NCCN-Compliant Multidisciplinary Conference on Treatment Decisions for Localized Prostate Cancer.

BACKGROUND: We sought to investigate the impact of an NCCN-compliant multidisciplinary conference on treatment decisions of patients with localized prostate cancer. METHODS: A retrospective review of our quality assurance localized prostate cancer database was performed. All patients with localized prostate cancer who sought a second opinion at Roswell Park Comprehensive Cancer Center between 2009 and 2019 were presented to the multidisciplinary Localized Prostate Cancer Conference (LPCC) that includes urologists, radiation oncologists, pathologists, and patient advocates. Multivariable regression models were fit to evaluate variables associated with concordance between community recommendations, LPCC recommendations, and treatment received by patients. RESULTS: A total of 1,164 patients were identified, of whom 26% had NCCN very low-/low-risk, 27% had favorable intermediate-risk, 25% had unfavorable intermediate-risk, and 22% had high-/very high-risk prostate cancer. Pathology changed in 11% of patients after genitourinary pathologist review, which caused disease reclassification in 9%. Concordance between community and LPCC recommendations occurred in 78%, with lowest concordance for androgen deprivation therapy (21%) and radiotherapy (53%). Concordance between community recommendations and treatment received occurred in 65%, with lowest concordance for androgen deprivation therapy and radiotherapy; among those who were recommended radiotherapy as the only option by their community urologist, only 26% received it. Concordance between LPCC recommendations and treatment received occurred in 92%. CONCLUSIONS: Community recommendations differed from the multidisciplinary NCCN-compliant recommendations in 22% of patients, primarily for radiotherapy. Multidisciplinary recommendations matched the treatment received in 92% of patients compared with 65% for community recommendations.

Does the urinary microbiome profile change after treatment of bladder cancer?

INTRODUCTION: We sought to investigate the change in the urinary microbiome profile after transurethral resection of bladder tumor (TURBT). METHODS: Urine specimens were collected from consecutive patients with bladder cancer. Patients were divided into those with bladder tumors ("Tumor group": de novo tumors or recurrent/progressed after TURBT ± intravesical therapy) versus those without evidence of recurrence after treatment "No Recurrent Tumor group". Samples were analyzed using 16S rRNA sequencing. Alteration in the urinary microbiome was described in terms of alpha (diversity within a sample measured by Observed, Chao, Shannon, and Simpson indices), beta diversities (diversity among different samples measured by Brady Curtis Diversity index), and differential abundance of bacteria at the genus level. Analyses were adjusted for gender, method of preservation (frozen vs preservative), and method of collection (mid-stream vs. catheter). RESULTS: Sixty-eight samples were analyzed (42 in "Tumor" vs 26 in "No Recurrent Tumor" groups). The median age was 70 years (IQR 64-74) and 85% were males. All patients in the "No Recurrent Tumor" group had non-muscle invasive bladder cancer and 85% received BCG compared to 69% and 43% for the "Tumor" group, respectively. There was no significant difference in alpha diversity (p > 0.05). Beta diversity was significantly different (p = 0.04). Veillonella and Bifidobacterium were more abundant in the "Tumor" group (> 2FC, p = 0.0002), while Escherichia-Shigella (> 2FC, p = 0.0002) and Helococcus (> 2FC, p = 0.0008) were more abundant in the "No Recurrent Tumor" group. CONCLUSION: Bladder cancer patients with no recurrence and/or progression exhibited a different urinary microbiome profile compared to those with tumors.

Utilizing Grasp Monitoring to Predict Microsurgical Expertise.

INTRODUCTION: Most microsurgical procedures require the surgeon to use tools to grasp and hold fragile objects in the surgical site. Prior research on grasping in surgery has mostly either been in other surgical techniques or used grasping as an auxiliary metric. We focus on microsurgery and investigate what grasping can tell about microsurgical skill and suturing performance. This study lays groundwork for using automatic detection of grasps to evaluate surgical skill. METHODS: Five expert surgeons and six novices completed sutures on a microsurgical training board. Video recordings of the performance were annotated for the number of grasps, while an eye tracker recorded the participants' pupil dilations for cognitive workload assessment. Performance was measured with suturing duration and the University of Western Ontario Microsurgical Skills Assessment instrument (UWOMSA). Differences in skill, suturing performance and cognitive workload were compared with grasping behavior. RESULTS: Novices needed significantly more grasps to complete sutures and failed to grasp more often than the experts. The number of grasps affected the suturing duration more in novices. Decreasing suturing efficiency as measured by UWOMSA instrument was associated with increase in grasps, even when we controlled for overall skill differences. Novices displayed larger pupil dilations when averaged over a sufficiently large sample, and the difference increased after the grasp. CONCLUSIONS: Grasping action during microsurgical procedures can be used as a conceptually simple yet objective proxy in microsurgical performance assessment. If the grasps could be detected automatically, they could be used to aid in computational evaluation of surgical trainees' performance.

The impact of preoperative ultrasound and intraoperative findings on surgical outcomes in patients at high risk of placenta accreta spectrum.

OBJECTIVE: To assess whether preoperative ultrasound imaging and intraoperative features predict surgical outcomes in patients at high risk for placenta accreta spectrum (PAS). DESIGN: Cohort study. SETTING: Cairo University Maternity, Egypt. POPULATION OR SAMPLE: Pregnant patients with one or more prior caesarean deliveries presenting with a low-lying/placenta praevia with or without PAS confirmed by histopathology. METHODS: Logistic regression and multivariable analyses. MAIN OUTCOMES MEASURES: Need for primary caesarean hysterectomy, numbers of red blood cell (RBC) units transfused and patients requiring transfusion of >5 units. RESULTS: Ninety consecutive records were reviewed, including 58 (64.4%) PAS cases. Sixty (66.7%, 95% confidence interval (CI) 56-76) required hysterectomy. Odds of hysterectomy were significantly (p = 0.005) increased with complete praevia. Significantly higher odds of hysterectomy were associated with subplacental hypervascularity (7.23, 95% CI 2.72-19.2, p < 0.001), lacunar scores 2+ and 3+ (12.6, 95% CI 4.15-38.5, p < 0.001), lacunar feeder vessels (5.69, 95% CI 1.77-18.3, p = 0.004) or bridging vessels (2.00, 95% CI 1.29-3.10, p = 0.002) on ultrasound, and increased lower segment vascularization at laparotomy (5.42, 95% CI 2.09-14.1, p = 0.001). Transfusion >5 RBC units was associated with number of lacunae (odds ratio [OR] 1.48, 95% CI 1.14-1.93, p = 0.004) and presence of feeder vessels (OR 1.62, 95% CI 1.24-2.11, p = 0.001). The multivariable analysis indicated that parity, placental location and PAS were significantly (p = 0.007; p = 0.01; p < 0.001, respectively) associated with hysterectomy. CONCLUSIONS: Preoperative ultrasound imaging can assist in triaging and counselling patients regarding the odds of PAS, intraoperative blood losses and need for hysterectomy, and intraoperative features can assist the surgeon in evaluating the need for multidisciplinary support.

Electrophysiological evaluation following development of new and persistent left bundle branch block after transcatheter aortic valve replacement: A single center pilot study.

INTRODUCTION: New and persistent left bundle branch block (NP-LBBB) following Transcatheter Aortic Valve Replacement (TAVR) is an ongoing concern with incidence ranging from as low as 4% to up to 65% (varying for different types of valves). Such patients are at risk of developing high-grade atrioventricular block (HAVB) warranting permanent pacemaker (PPM) implantation. However, currently, there are no consensus guidelines or large prospective studies to risk stratify these patients for safer discharge after TAVR. OBJECTIVES: To provide insight from a single center study on using modified electrophysiology (EP) study to risk stratify post-TAVR patients to outpatient monitoring for low-risk versus pacemaker implantation for high-risk patients. METHODS AND RESULTS: Between June 2020 and March 2023, all patients who underwent a TAVR procedure (324 patients) at our institution were screened for development of NP-LBBB post-operatively. Out of 26 patients who developed NP-LBBB, after a pre-specified period of observation, 18 patients were deemed eligible for a modified EP study to assess His-Ventricular (HV) interval. 11 out of 18 patients (61.1%) had normal HV interval (HV < 55 ms). Three out of 18 patients (16.7%) had HV prolongation (55 ms < HV < 70 ms) without significant HV prolongation (defined as an increase in HV interval > 30%) with intra-procedural procainamide challenge. Four out of 18 patients (22.2%) had significant HV prolongation (HV > 70 ms) warranting PPM implantation based on a multidisciplinary approach and shared decision-making with the patients. Total of 50% of patients discharged with PPM (two out of four patients) were noted to be pacemaker dependent based on serial device interrogations. All patients who did not receive PPM were discharged with ambulatory monitoring with 30-day event monitor and did not develop HAVB on serial follow-up. CONCLUSION: Normal HV interval up to 55 ms on modified EP study after TAVR and development of NP-LBBB can be utilized as a threshold for risk stratification to facilitate safe discharge. The optimal upper limit of HV interval threshold remains unclear in determining appropriate candidacy for PPM.

Anterior occipital condyle screw placement through the endonasal corridor: proof of concept study with cadaveric analysis.

PURPOSE: Odontoidectomy for ventral compressive pathology may result in O-C1 and/or C1-2 instability. Same-stage endonasal C1-2 spinal fusion has been advocated to eliminate risks associated with separate-stage posterior approaches. While endonasal methods for C1 instrumentation and C1-2 trans-articular stabilization exist, no hypothetical construct for endonasal occipital instrumentation has been validated. We provide an anatomic description of anterior occipital condyle (AOC) screw endonasal placement as proof-of-concept for endonasal craniocervical stabilization. METHODS: Eight adult, injected cadaveric heads were studied for placing 16 AOC screws endonasally. Thin-cut CT was used for registration. After turning a standard inferior U-shaped nasopharyngeal flap endonasally, 4 mm × 22 mm AOC screws were placed with a 0° driver using neuronavigation. Post-placement CT scans were obtained to determine: site-of-entry, measured from the endonasal projection of the medial O-C1 joint; screw angulation in sagittal and axial planes, proximity to critical structures. RESULTS: Average site-of-entry was 6.88 mm lateral and 9.74 mm rostral to the medial O-C1 joint. Average angulation in the sagittal plane was 0.16° inferior to the palatal line. Average angulation in the axial plane was 23.97° lateral to midline. Average minimum screw distances from the jugular bulb and hypoglossal canal were 4.80 mm and 1.55 mm. CONCLUSION: Endonasal placement of AOC screws is feasible using a 0° driver. Our measurements provide useful parameters to guide optimal placement. Given proximity of hypoglossal canal and jugular bulb, neuronavigation is recommended. Biomechanical studies will ultimately be necessary to evaluate the strength of AOC screws with plate-screw constructs utilizing endonasal C1 lateral mass or C1-2 trans-articular screws as inferior fixation points.

Development and validation of nomogram to improve the specificity of multiparametric MRI for clinically significant prostate cancer.

OBJECTIVE: To develop and validate a nomogram to improve the specificity of prostate imaging reporting and data system (PI-RADS) on multiparametric magnetic resonance imaging (MRI) for clinically significant prostate cancer on targeted fusion biopsy. METHODS: A retrospective review of patients who underwent fusion biopsy for PI-RADS 3-5 lesions using UroNav and Artemis systems between 2016 and 2022 was performed. Patients were divided into those with CS disease on fusion biopsy (Gleason grade group ≥2) versus those without. Multivariable analysis was used to identify variables associated with CS disease. A 100-point nomogram was constructed, and ROC curve was generated. RESULTS: 1485 lesions (1032 patients) were identified, 510 (34%) were PI-RADS 3, 586 (40%) were PI-RADS 4, and 389 (26%) were PI-RADS 5. Of these, 11% of PI-RADS 3, 39% of PI-RADS 4, and 61% of PI-RADS 5 showed CS disease. CS disease was associated with older age (OR 1.04, 95% CI 1.02-1.06, p < 0.01), previous negative biopsy (OR 0.52, 95% CI 0.36-0.74, p < 0.01), presence of multiple PI-RADS 3-5 lesions (OR 0.61, 95% CI 0.45-0.83, p < 0.01), peripheral zone location (OR 1.88, 95% CI 1.30-2.70, p < 0.01), PSA density (OR 1.48 per 0.1 unit, 95% CI 1.33-1.64, p < 0.01), PI-RADS score 4 (OR 3.28, 95% CI 2.21-4.87, p < 0.01), and PI-RADS score 5 (OR 7.65, 95% CI 4.93-11.85, p < 0.01). Area under ROC curve was 82% for nomogram compared to 75% for PI-RADS score alone. CONCLUSION: We report a nomogram that combines PI-RADS score with other clinical parameters. The nomogram outperforms PI-RADS score for the detection of CS prostate cancer.

An Innovative Low-Power, Low-Cost, Multi-Constellation Geodetic-Grade Global Navigation Satellite System Reference Station for the Densification of Permanent Networks: The GREAT Project.

Geodetic-grade Global Navigation Satellite System (GNSS) receivers designed to implement permanent stations represent the most complex and costly technology in the field of GNSS instrumentation. On the other hand, a large number of innovative applications, highly demanding in terms of positioning precision and accuracy, is pushing the implementation of networks of permanent stations with a higher and higher spatial density. In this scenario, the development of brand new GNSS reference stations, which combine the most advanced technologies in the field of data availability and integrity together with reduced costs (of instrumentation, installation and management) is becoming of paramount importance. For this reason, in 2019 the EU Agency for the Space Programme (EUSPA) has financed a research project, called "next Generation gnss REference stATion-GREAT", aimed at developing and demonstrating the potentiality of a brand new GNSS receiver suitable to implement permanent stations. This paper describes the solution developed by the project consortium, composed of four Small or Medium Enterprises (SMEs) based in Italy, France and Belgium, and the preliminary results achieved in the field tests.

Analysis of Three Species of Cassipourea Traditionally Used for Hypermelanosis in Selected Provinces in South Africa.

There is a growing demand and use of herbal cosmetics for skin purposes due to their perceived safety when applied to the skin. Three Cassipourea species commonly known as "ummemezi" are used interchangeably by women in rural areas of Eastern Cape and KwaZulu-Natal provinces to treat hypermelanosis as well as sun protection. We conducted a phytochemical comparison of three Cassipourea species; Cassipourea flanaganii (Schinz) Alston, Cassipourea gummiflua Tul. verticillata (N.E.Br.) J. Lewis and Cassipourea malosana (Baker) Alston by Liquid Chromatography-Mass Spectrometry (LC-MS/MS) analysis in negative mode. The results obtained from the LC-MS/MS yielded a total number of twenty-four compounds of different chemical classes, including fatty acids, steroids, di- and tri-terpenoids, flavonoids, phenolic acids, and eighteen among them were tentatively identified. The LC-MS /MS analysis showed that the three studied Cassipourea extracts contain compounds that have anti-tyrosinase activity and consequently. The presence of these compounds, either in synergy or individually, can be attributed to the anti-tyrosinase effect. Although the traditional names of the species are used interchangeably, they are different, however, they possess similar skin-lightening properties. Despite the recent popularity of modern cosmetic products, plants continue to play an important role in the local cosmetics industry in South Africa's Eastern Cape and KwaZulu-Natal community provinces.

Proteolytic Activation of the Epithelial Sodium Channel (ENaC): Its Mechanisms and Implications.

Epithelial sodium channel (ENaC) are integral to maintaining salt and water homeostasis in various biological tissues, including the kidney, lung, and colon. They enable the selective reabsorption of sodium ions, which is a process critical for controlling blood pressure, electrolyte balance, and overall fluid volume. ENaC activity is finely controlled through proteolytic activation, a process wherein specific enzymes, or proteases, cleave ENaC subunits, resulting in channel activation and increased sodium reabsorption. This regulatory mechanism plays a pivotal role in adapting sodium transport to different physiological conditions. In this review article, we provide an in-depth exploration of the role of proteolytic activation in regulating ENaC activity. We elucidate the involvement of various proteases, including furin-like convertases, cysteine, and serine proteases, and detail the precise cleavage sites and regulatory mechanisms underlying ENaC activation by these proteases. We also discuss the physiological implications of proteolytic ENaC activation, focusing on its involvement in blood pressure regulation, pulmonary function, and intestinal sodium absorption. Understanding the mechanisms and consequences of ENaC proteolytic activation provides valuable insights into the pathophysiology of various diseases, including hypertension, pulmonary disorders, and various gastrointestinal conditions. Moreover, we discuss the potential therapeutic avenues that emerge from understanding these mechanisms, offering new possibilities for managing diseases associated with ENaC dysfunction. In summary, this review provides a comprehensive discussion of the intricate interplay between proteases and ENaC, emphasizing the significance of proteolytic activation in maintaining sodium and fluid balance in both health and disease.