The implementation status of prehabilitation during neoadjuvant chemotherapy for patients with locally advanced esophageal cancer: a questionnaire survey to the board-certified facilities in Japan.

BACKGROUND: Prehabilitation during neoadjuvant therapy has the potential to improve clinical outcomes. However, information on its global dissemination status is limited. This Japanese nationwide survey investigated the implementation status of and barriers to prehabilitation during neoadjuvant chemotherapy (NAC) for patients with locally advanced esophageal cancer in hospitals. METHODS: This multicenter nationwide survey was conducted by post. The eligible facilities were 155 Japanese hospitals that had been certified within the last 10 years as authorized institutes for board-certified esophageal surgeons by the Japan Esophageal Society. We administered an original questionnaire to investigate the current status of prehabilitation during NAC. RESULTS: The response rate was 75% (117/155 facilities). Forty-six facilities (39%) provided prehabilitation during NAC. The most frequently selected reasons for not providing or providing insufficient prehabilitation were lack of human resources, issues with the reimbursement of medical fees, difficulty in providing continuous prehabilitation during repeated inpatient and outpatient care, the lack of established standard prehabilitation programs, challenges in providing multidisciplinary prehabilitation, and difficulty in managing physical symptoms. CONCLUSION: We observed that the implementation rate of prehabilitation during NAC was low. Critical reasons were not only the lack of medical resources but also the lack of evidence-based standard prehabilitation programs during NAC and the lack of evidence for how to continuously deliver prehabilitation during NAC to patients with physical symptoms.

Regulatory effects of antioxidants on indoxyl sulfate-enhanced intracellular oxidation and impaired phagocytic activity in differentiated U937 human macrophage cells.

Indoxyl sulfate (IS), a uremic toxin, is a physiologically active sulfated metabolite, specifically in kidney failure patients. Our previous studies have shown that IS downregulates phagocytic immune function in a differentiated HL-60 human macrophage cell model. However, it remains unclear whether IS exerts similar effects on macrophage function in other cell types or in lipopolysaccharide (LPS)-sensitive immune cell models. Therefore, this study aimed to investigate the effects of IS on intracellular oxidation levels and phagocytic activity in a differentiated U937 human macrophage cell model, both in the absence and presence of LPS. Our results demonstrated that IS significantly increases intracellular oxidation levels and decreases phagocytic activity, particularly in cells activated by LPS. Furthermore, we found that 2-acetylphenothiazine, an NADH oxidase inhibitor, attenuates the effects of IS in LPS-activated macrophage cells. Representative antioxidants, trolox, α-tocopherol, and ascorbic acid, significantly mitigated the effects of IS on the macrophages responding to LPS.

Effectiveness of prehabilitation during neoadjuvant therapy for patients with esophageal or gastroesophageal junction cancer: a systematic review.

Progression of the physical weakness during neoadjuvant therapy (NAT) in patients with esophageal or gastroesophageal junction cancer is a serious problem; however, prehabilitation during NAT has the potential to overcome the unmet need. Nevertheless, systematic reviews on this topic have not been summarized. Therefore, this systematic review aimed to determine prehabilitation's effectiveness, acceptability, and safety during NAT for patients with esophageal or gastroesophageal junction cancer. An electronic search was performed in the MEDLINE, Web of Science, CENTRAL, CINAHL, and PEDro databases. A meta-analysis was conducted to assess the effectiveness of prehabilitation during NAT, along with a descriptive analysis of acceptance and safety. This study analyzed data from three randomized controlled trials (RCTs) and nine non-RCTs involving 664 patients. The meta-analysis of two RCTs demonstrated that prehabilitation during NAT may be more effective than usual care in enhancing tolerance to NAT and grip strength; moreover, one RCT and three non-RCTs revealed that prehabilitation may reduce the risk of postoperative complications. The adherence rates for exercise programs in two RCTs and seven non-RCTs were 55-76%. Additionally, two studies reported a 76% adherence rate for multimodal prehabilitation programs, including exercise, dietary, and psychological care. Six studies reported no serious prehabilitation-related adverse events during NAT. Prehabilitation during NAT may be a safe and beneficial intervention strategy for patients with esophageal or gastroesophageal junction cancer. However, the investigation of strategies to enhance adherence is essential. Furthermore, additional high-quality RCTs are needed to examine the effect of prehabilitation during NAT.

Analysis of respiratory-induced motion trajectories of individual liver segments in patients with hepatocellular carcinoma.

PURPOSE: To analyze the respiratory-induced motion trajectories of each liver segment for hepatocellular carcinoma (HCC) to derive a more accurate internal margin and optimize treatment protocol selection. MATERIALS AND METHODS: Ten-phase-gated four-dimensional computed tomography (4DCT) scans of 14 patients with HCC were analyzed. For each patient, eight representative regions of interest (ROI) were delineated on each liver segment in all 10 phases. The coordinates of the center of gravity of each ROI were obtained for each phase, and then the respiratory motion in the left-right (LR), anteroposterior (AP), and craniocaudal (CC) directions was analyzed. Two sets of motion in each direction were also compared in terms of only two extreme phases and all 10 phases. RESULTS: Motion of less than 5 mm was detected in 12 (86%) and 10 patients (71%) in the LR and AP directions, respectively, while none in the CC direction. Motion was largest in the CC direction with a maximal value of 19.5 mm, with significant differences between liver segment 7 (S7) and other segments: S1 (p < 0.036), S2 (p < 0.041), S3 (p < 0.016), S4 (p < 0.041), and S5 (p < 0.027). Of the 112 segments, hysteresis >1 mm was observed in 4 (4%), 2 (2%), and 15 (13%) in the LR, AP, and CC directions, respectively, with a maximal value of 5.0 mm in the CC direction. CONCLUSION: A significant amount of respiratory motion was detected in the CC direction, especially in S7, and S8. Despite the small effect of hysteresis, it can be observed specifically in the right lobe. Therefore, caution is required when using 4DCT to determine IM using only end-inspiration and end-expiration. Understanding the respiratory motion in individual liver segments can be helpful when selecting an appropriate treatment protocol.

Effects of Nutritional Support Combined with Neuromuscular Electrical Stimulation on Muscle Strength and Thickness: A Randomized Controlled Trial in Healthy Young Adult Males.

In the management of post-injury patients with activity limitations, methods to prevent musculoskeletal disorders and hasten recovery are important. This randomized controlled, single-blinded study was a preliminary investigation of the combined effect of nutritional support with neuromuscular electrical stimulation (NMES) on muscle strength and thickness. Healthy young adult males (median age, 21 years) were enrolled; each of their hands was randomly assigned to one of the following four groups: Placebo, Nutrition, NMES, and Nutrition + NMES. All participants received whey protein or placebo (3x/week for 6 weeks) and NMES training (3x/week for 6 weeks) on the abductor digiti minimi (ADM) muscle of either the left or right hand. ADM muscle strength and thickness were analyzed at baseline and at week 7. We analyzed 38 hands (9 Placebo, 10 Nutrition, 9 NMES, 10 Nutrition + NMES). There was significantly greater muscle strengthening in the Nutrition + NMES group compared to the Placebo group or the NMES group, but no significant difference in gain of muscle thickness. The combined intervention may be effective in improving muscle strength. Future clinical trials targeting various muscles after sports-related injuries are warranted.

Effects of microsampling on toxicity evaluation of 1-naphthylisothiocyanate (ANIT), a hepatotoxic substance, in a mouse toxicity study.

ICH S3A Q&A focused on microsampling (MS) was published to help accelerate the use of MS and states that MS is useful because toxicokinetic (TK) evaluation with conventional blood sampling volume requires many animals for TK satellite groups; however, there are few reports of MS application in mice. We investigated the influence of MS on toxicity evaluation in mice by comparing the toxicity parameters with and without MS after a single oral administration of 1-naphthylisothiocyanate (ANIT), a hepatotoxic substance. Blood samples (50 µL/point) were collected from the tail vein of 3 mice per group at 2 or 3 time points during a 24-hr period, and toxicity was evaluated 2 days after administration. ANIT-related changes suggesting liver or gallbladder injury were noted in blood chemistry and histopathology. Some of these changes such as increases in focal hepatocyte necrosis and inflammatory cell infiltration in the liver as well as mucosal epithelium necrosis in the gallbladder were apparently influenced by MS. A tendency to anemia was noted in animals with MS but not without MS, which was also noted in the vehicle-treated controls, suggesting influence of blood loss. The current results indicate that ANIT hepatotoxicity could be evaluated in mice in which blood samples were collected by MS for most parameters; however, parameters in anemia and pathology in the liver and gallbladder were influenced by MS in this study condition with ANIT. Therefore, MS application in mice should be carefully considered.

Dosimetric effect of six degrees of freedom couch top with rotational setup error corrections in proton therapy.

PURPOSE: To investigate the dosimetric effect of six degrees of freedom (6DoF) couch top with rotational corrections in proton therapy (PT). METHODS: The water equivalent thickness (WET) was measured using a proton beam with a 6DoF couch top and patient immobilization base plate (PIBP) placed in front of a motorized water phantom. The accuracy verification was performed with the beam axis set perpendicular to the 6DoF couch top and tilted in 10° steps from 10° to 30°. Up to 3° rotational correction may be added during the actual treatment to correct the rotational setup error on our system. The measured and calculated values using the treatment planning system were compared. Additionally, the effect of the 3° difference was evaluated using actual measurements concerning each angle on the proton beam range. RESULTS: The WET of the 6DoF couch top and PIBP were 8.5 ± 0.1 mm and 6.8 ± 0.1 mm, respectively. The calculation and the actual measurement at each angle agreed within 0.2 mm at the maximum. A maximum difference of approximately 0.6 mm was confirmed when tilted at 3° following 30° with the 6DoF couch top plus PIBP. CONCLUSIONS: The dosimetric effect of the 6DoF couch top with rotational corrections in PT differs depending on the incidence angle on the couch top, and it increased with the increased oblique angle of incidence. However, the effect on the range was as small as 0.6 mm at the maximum. The amount of rotational correction, the angle of incidence of the beam, and the effect of rotational corrections on the proton beam range may differ depending on the structure of the couch top. Therefore, sufficient prior confirmation, and subsequent periodical quality assurance management are important.

Validity of the 30-Second Chair-Stand Test to Assess Exercise Tolerance and Clinical Outcomes in Patients with Esophageal Cancer: A Retrospective Study with Reference to 6-Minute Walk Test Results.

This retrospective study aimed to investigate the validity of a 30-sec chair stand test (CS-30) as a simple test to assess exercise tolerance and clinical outcomes in 53 Japanese patients with esophageal cancer. There was a strong correlation between the results of CS-30 and the 6-min walk test (6MWT), the gold standard for assessing exercise tolerance (r=0.759). Furthermore, fewer patients whose CS-30 score was greater than 16 (the cutoff value defined based on 6MWT) experienced pneumonia in their postoperative course. These results suggest that exercise tolerance could be assessed using CS-30, and its cutoff value may be useful in predicting postoperative pneumonia risk.

The combined intervention of neuromuscular electrical stimulation and nutrition therapy: A scoping review.

BACKGROUND & AIMS: Neuromuscular electrical stimulation (NMES) is a safe and appropriate complement to voluntary resistance training for muscle weakness. However, its feasibility and effectiveness in combination with nutritional therapy remains unclear. This scoping review aimed to summarize the evidence on combined interventions for individuals with or at risk of sarcopenia for guiding future relevant research. METHODS: A systematic electronic search was conducted using the following databases and registry: MEDLINE, CINAHL, Web of Science, PEDro, and ClinicalTrials. gov. Two independent reviewers summarized the characteristics, effectiveness, and feasibility of the combined intervention and the risk of bias in the literature. RESULTS: Nine RCTs and four non-RCTs involving 802 participants were eligible. A diverse group of participants were included: older adults with sarcopenic obesity, patients in intensive care, and patients with cancer. Evidence-based interventions combining NMES and nutritional therapy were tailored to each patient's underlying disease. Although most studies were of low to moderate quality, it can be suggested that combined interventions may be feasible and effective for increasing skeletal muscle mass. CONCLUSION: This scoping review demonstrates the potential of combined interventions as a new sarcopenia treatment strategy and highlights the need to examine the effects in high-quality RCTs with larger sample sizes.

Protocol for a randomised, placebo-controlled, double-blinded clinical trial on the effect of oestrogen replacement on physical performance to muscle resistance exercise for older women with osteoarthritis of knee joint: the EPOK trial.

BACKGROUND: Knee osteoarthritis (KOA) is highly prevalent in older women, and previous studies suggest the involvement of hormonal factors play a role in the pathogenesis of osteoarthritis. KOA causes musculoskeletal impairment, resulting in decreased physical activity, muscle mass, and strength, which leads to sarcopenia and further increases the burden on healthcare systems. Oestrogen replacement therapy (ERT) improves joint pain and muscle performance in early menopausal women. Muscle resistance exercise (MRE) is a non-pharmacological method that preserves the physical functions of patients with KOA. However, data on short-term oestrogen administration combined with MRE in postmenopausal women, especially in those aged > 65 years, are limited. Therefore, this study presents a protocol of a trial aimed to examine the synergistic effect of ERT and MRE on lower-limb physical performance in older women with KOA. METHODS: We will conduct a double-blinded, randomised placebo-controlled trial in 80 Japanese women aged > 65 years living independently with knee pain. The participants will be randomly categorised into two groups: (1) 12-week MRE programme with transdermal oestrogen gel containing 0.54 mg oestradiol per push and (2) 12-week MRE programme with placebo gel. The primary outcome measured using the 30-s chair stand test, and secondary outcomes (body composition, lower-limb muscle strength, physical performance, self-reported measure of knee pain, and quality of life) will be measured at baseline, 3 months, and 12 months, and these outcomes will be analysed based on the intention-to-treat. DISCUSSION: The EPOK trial is the first study to focus on the efficacy of ERT on MRE among women aged > 65 years with KOA. This trial will provide an effective MRE to prevent KOA-induced lower-limb muscle weakness, confirming the benefit of short-term oestrogen administration. TRIAL REGISTRATION: Japan Registry of Clinical Trials: jRCTs061210062. Registered 17th December 2021, https://jrct.niph.go.jp/en-latest-detail/jRCTs061210062 .

Effectiveness of early exercise on reducing skeletal muscle loss during preoperative neoadjuvant chemotherapy for esophageal cancer.

PURPOSE: To investigate if early exercise can help prevent skeletal muscle loss and improve the clinical outcomes of esophageal cancer patients receiving preoperative neoadjuvant chemotherapy (NAC). METHODS: This was a single-center, retrospective observational cohort study of 110 patients with advanced esophageal cancer. We analyzed the effect of early exercise on the risk of skeletal muscle loss (defined as > 2.98%) during NAC and the subsequent clinical outcomes. Patients in the early exercise group (n = 71) started exercise therapy 8 days earlier than those the late exercise group (n = 39). RESULTS: The median age of the patients was 65.4 years, the mean BMI was 21.1 kg/m2, and 92 (84%) of the 110 patients were men. Skeletal muscle loss occurred in 34% and 67% of the early and late exercise groups, respectively (p < 0.001). There was a lower risk of surgical site infection in the early exercise group (1% vs 16%, p = 0.021). Multivariate analysis revealed that early exercise reduced the risk of skeletal muscle loss (OR = 0.25, 95% CI 0.09-0.65, p = 0.006). CONCLUSIONS: Our results suggest that early exercise reduces the risk of both skeletal muscle loss during NAC and subsequent surgical site infection in patients with esophageal cancer.

Classification of medial longitudinal arch kinematics during running and characteristics of foot muscle morphology in novice runners with pronated foot.

BACKGROUND: Novice runners with pronated feet are at an increased risk of running-related injuries. However, not all runners with pronated feet have increased foot pronation during running. Moreover, although foot muscle morphology is related to static foot alignment, the relationship between foot muscle morphology and foot kinematics during running remains unclear. We aimed to determine foot kinematic patterns during running among novice runners with pronated feet and the presence of a relationship between these foot kinematic patterns and foot muscle morphology. METHODS: Twenty-one novice runners with pronated feet participated in this study, and data on 39 lower limbs were collected. Data on foot kinematics during running (rearfoot strike) were collected using a three-dimensional motion capture system in terms of navicular height (NH) at initial contact and dynamic navicular drop (DND). A hierarchical cluster analysis method was used to identify the optimal number of clusters based on these two foot-related kinematic variables. Following identification of the clusters, differences in cluster variables and cross-sectional areas of selected foot muscles assessed using ultrasonography in each cluster were examined. The muscles of interest included the abductor hallucis, flexor hallucis brevis and longus, flexor digitorum brevis and longus, and peroneus longus. RESULTS: Three subgroups were identified based on foot kinematics during running: cluster 1, lowest NH at initial contact and larger DND; cluster 2, moderate NH at initial contact and smaller DND; and cluster 3, highest NH at initial contact and larger DND. Clusters 1 and 3 had a larger abductor hallucis compared with cluster 2, and cluster 3 had a larger flexor hallucis brevis compared with cluster 2. SIGNIFICANCE: These subgroups may differ in terms of resistance to and type of running-related injury. Moreover, foot kinematics during running is possibly impacted by the morphology and function of medial intrinsic foot muscles.

Risk factors for readmission in schizophrenia treated with combined psychoeducation and standard therapy.

BACKGROUND: We conducted a historical cohort study of patients with schizophrenia to identify more robust risk factors at discharge that contribute to readmission within a year. METHODS AND FINDINGS: The subjects underwent brief psychoeducation during hospitalization. Multivariate analysis was conducted using factors selected in the univariate analysis. Using logistic regression analysis, the number of hospital admissions (P = .01) and Schedule for Assessment of Insight Japanese version score (P = .04) were identified as risk factors for readmission, with odds ratios of 0.70 and 1.18, respectively. CONCLUSIONS: These results suggest that improvement in insight and early intervention may lead to a more stable community life.

Dosimetric impact of simulated changes in large bowel content during proton therapy with simultaneous integrated boost for locally advanced pancreatic cancer.

PURPOSE: To investigate the dosimetric impact of changes in the large bowel content during proton therapy (PT) with simultaneous integrated boost (SIB) for locally advanced pancreatic cancer (LAPC). MATERIALS AND METHODS: Fifteen patients with LAPC were included in this study. The SIB method was performed using five fields according to our standard protocol. A total dose of 67.5 Gy(relative biological effectiveness [RBE]) was prescribed in 25 fractions using the SIB method. A dose of 45 Gy(RBE) was prescribed for the entire planning target volume (PTV) by using four main fields. The remaining 22.5 Gy(RBE) was prescribed to the PTV excluding for the gastrointestinal tract using one subfield. Five simulated doses were obtained by the forward dose calculations with the Hounsfield units (HU) override to the large bowel to 50, 0, -100, -500, and -1000, respectively. The dose-volume indices in each plan were compared using the 50 HU plan as a reference. RESULTS: At D98 of the clinical target volume (CTV) and spinal cord-D2cc , when the density of the large bowel was close to that of gas, there were significant differences compared to the reference plan (p < 0.05). By contrast, no significant difference was observed in stomach-D2cc duodenum-D2cc , small bowel-D2cc , kidneys-V18 , and liver-Dmean under any of the conditions. There were no cases in which the dose constraint of organs at risk, specified by our institution, was exceeded. CONCLUSION: Density change in the large bowel was revealed to significantly affect the doses of the CTV and spinal cord during PT with SIB for LAPC. For beam arrangement, it is important to select a gantry angle that prevents the large bowel from passing as much as possible. If this is unavoidable, it is important to carefully observe the gas image on the beam path during daily image guidance and to provide adaptive re-planning as needed.

Relationship between foot muscle morphology and severity of pronated foot deformity and foot kinematics during gait: A preliminary study.

BACKGROUND: The morphology of foot muscles that support the medial longitudinal arch differs between normal and pronated feet. The degree to which the difference depends on the severity of the pronated foot deformity is unclear. In the clinical setting, however, to reduce the pronated deformity, muscle-strengthening exercises are performed. RESEARCH QUESTION: Does a relationship exist between foot muscle morphology and severity of the pronated foot deformity and foot kinematics during gait? METHODS: Using the six-item foot posture index (FPI-6), 26 study participants were assessed for their foot posture and divided into two groups of 13 participants each based on the FPI-6 score: pronated foot group (with a score of 6-9) and highly pronated foot group (with a score of 10-12). Select foot muscles were scanned with ultrasonography, and muscle thicknesses were measured. The following were the muscles of interest: abductor hallucis, flexor hallucis brevis and longus, flexor digitorum brevis and longus, and peroneus longus. Foot kinematic data during gait was collected using a three-dimensional motion capture system as a dynamic navicular drop. RESULTS: No between-group differences were noted for muscle thickness and dynamic navicular drop. However, the abductor hallucis and flexor hallucis brevis thicknesses were correlated with the dynamic navicular drop, but not with the severity of the pronated foot deformity. SIGNIFICANCE: In individuals with pronated foot deformity, more developed abductor hallucis and flexor hallucis brevis muscles may reduce the dynamic navicular drop that represents the degree of medial longitudinal arch deformation during the stance phase of gait.

Conventional Trabeculotomy versus Gonioscopy-Assisted Transluminal Trabeculotomy: A Retrospective Cohort Study.

BACKGROUND: Conventional trabeculotomy (CT) is performed in an ab-externo manner with at most 120 degrees of incision area of Schlemm's canal (SC). Recently, gonioscopy-assisted transluminal trabeculotomy (GATT), which makes possible a 360-degree incision area of SC in an ab-interno manner, is introduced. The purpose of this study was to compare surgical outcomes for CT and GATT with and without simultaneous phacoemulsification over 24 months and to identify factors associated with surgical success. RESULTS: Patients' baseline characteristics were not significantly different between two groups. The surgical success rate in CT and GATT with phacoemulsification groups were 40.4% and 96.6% and were significantly higher in the GATT group than in the CT group (p < 0.001). However, the surgical success rate in CT and GATT without phacoemulsification groups were 40.8% and 54.2%, and there were no significant differences between two groups without phacoemulsification (p = 0.55). Similarly, the postoperative IOP was significantly lower in the GATT group than in the CT group only in eyes with simultaneous phacoemulsification. There were no significant differences in the numbers of glaucoma medications between the two groups. Additional glaucoma surgery was needed in 13.2% and 25.9% of patients in the GATT and CT groups, respectively (p = 0.157). The multivariate logistic regression analysis revealed that the surgical success of trabeculotomy was significantly associated with combined phacoemulsification and the type of glaucoma surgery (GATT). CONCLUSION: Although both groups without phacoemulsification had a similar surgical success and IOP-lowering effect, GATT combined with phacoemulsification had a higher surgical success rate and a greater IOP-lowering effect compared with combined CT and phacoemulsification. Multivariate logistic regression analysis showed that the factors associated with higher surgical success at one year and two years postoperatively were the combined phacoemulsification procedure and the GATT.

Progression of glaucomatous optic neuropathy associated with chorioretinal microvascular embolism after intranasal injection of a corticosteroid suspension.

A patient with glaucoma developed sudden blurred vision immediately after the nasal mucosal injection of a betamethasone acetate solution into the inferior turbinate. The fundus examination revealed several white emboli in the choroidal vessels of the temporal region of the optic disc. After vigorous massage, her visual acuity recovered from counting fingers to 20/32. Six days after the initial examination, Goldmann perimetry showed expansion of the superior and inferior arcuate scotomas. In this case, temporary ischemia of the central retinal and short posterior ciliary arteries involving the arterial circle of Zinn-Haller led to the deterioration of the preexisting glaucomatous optic neuropathy.

Intraocular pressure elevation after subtenon triamcinolone acetonide injection; Multicentre retrospective cohort study in Japan.

PURPOSE: To evaluate real-world evidence for intraocular pressure (IOP) elevation after subtenon triamcinolone acetonide injection (STTA) in 1252 Japanese patients (1406 eyes) in the Japan Clinical REtina STudy group (J-CREST). METHODS: This was a multicentre retrospective study of the medical records of 1252 patients (676 men (758 eyes); mean age: 63.8 ± 12.9 years) who received STTA in participating centres between April 2013 and July 2017. RESULTS: IOP elevation was observed in 206 eyes (14.7%) and IOP increase ≥ 6 mmHg was found in 328 eyes (23.3%). In total, 106 eyes (7.5%) needed medication and two eyes (0.14%) needed surgical procedures. Younger age, higher baseline IOP, and steroid dose were risk factors associated with IOP elevation. Risk factors associated with IOP increase ≥ 6 mmHg were younger age, lower baseline IOP, steroid dose, and higher incidences of diabetic macular oedema (DME) and uveitis. In contrast, with steroid dose fixed at 20 mg, a lower incidence of DME was a risk factor for increased IOP, suggesting that STTA had dose-dependent effects on IOP increase, especially in patients with DME. CONCLUSION: Our real-world evidence from a large sample of Japanese patients who received STTA showed that the incidence of IOP elevation after STTA was 14.7%, and was associated with younger age, higher baseline IOP, and steroid dose. Thus, IOP should be monitored, especially in patients with younger age, higher baseline IOP, and higher incidences of DME and uveitis.

Co(III) Complexes with N2S3-Type Ligands as Structural/Functional Models for the Isocyanide Hydrolysis Reaction Catalyzed by Nitrile Hydratase.

It has been before reported that, in addition to hydration of nitriles, the Fe-type nitrile hydratase (NHase) also catalyzes the hydrolysis of tert-butylisocyanide ( tBuNC). In order to investigate the unique isocyanide hydrolysis by NHase, we prepared three related Co(III) model complexes, PPh4[Co(L)] (1), PPh4[Co(L-O3)] (2), and PPh4[Co(L-O4)] (3), where L is bis( N-(2-mercapto-2-methylpropionyl)aminopropyl)sulfide. The suffixes L-O3 and L-O4 indicate ligands with a sulfenate and a sulfinate and with two sulfinates, respectively, instead of the two thiolates of L. The X-ray analyses of 1 and 3 reveal trigonal bipyramidal and square pyramidal structures, respectively. Complex 2, however, has five-coordinate trigonal-bipyramidal geometry with η2-type S-O coordination by a sulfenyl group. Addition of tBuNC to 1, 2, and 3 induces an absorption spectral change as a result of formation of an octahedral Co(III) complex. This interpretation is also supported by the crystal structures of PPh4[Co(L-O4)( tBuNC)] (4) and (PPh4)2[Co(L-O4)(CN)] (5). A water molecule interacts with 3 but cannot be activated as reported previously, as demonstrated by the lack of absorption spectral change in the pH range of 5.5-10.2. Interestingly, the coordinated tBuNC is hydrolyzed by 2 and 3 at pH 10.2 to produce tBuNH2 and CO molecule, but 1 does not react. These findings provide strong evidence that hydrolysis of tBuNC by NHase proceeds not by activation of the coordinated water molecule but by coordination of the substrate. The mechanism of the hydrolysis reaction of tBuNC is explained with support provided by DFT calculations; a positively polarized C atom of tBuNC on the Co(III) center is nucleophilically attacked by a hydroxide anion activated through an interaction of the sulfenyl/sulfinyl oxygen with the nucleophile.

An uncertainty metric to evaluate deformation vector fields for dose accumulation in radiotherapy.

BACKGROUND AND PURPOSE: In adaptive radiotherapy, deformable image registration (DIR) is used to propagate delineations of tumors and organs into a new therapy plan and to calculate the accumulated total dose. Many DIR accuracy metrics have been proposed. An alternative proposed here could be a local uncertainty (LU) metric for DIR results. MATERIALS AND METHODS: The LU represented the uncertainty of each DIR position and was focused on deformation evaluation in uniformly-dense regions. Four cases demonstrated LU calculations: two head and neck cancer cases, a lung cancer case, and a prostate cancer case. Each underwent two CT examinations for radiotherapy planning. RESULTS: LU maps were calculated from each DIR of the clinical cases. Reduced fat regions had LUs of 4.6 ±â€¯0.9 mm, 4.8 ±â€¯1.0 mm, and 4.5 ±â€¯0.7 mm, while the shrunken left parotid gland had a LU of 4.1 ±â€¯0.8 mm and the shrunken lung tumor had a LU of 3.7 ±â€¯0.7 mm. The bowels in the pelvic region had a LU of 10.2 ±â€¯3.7 mm. LU histograms for the cases were similar and 99% of the voxels had a LU < 3 mm. CONCLUSIONS: LU is a new uncertainty metric for DIR that was demonstrated for clinical cases. It had a tolerance of <3 mm.