Differences in the Impact of Intensive Rehabilitation on Hereditary Ataxias and the Cerebellar Subtype of Multiple System Atrophy.

Multiple system atrophy-cerebellar type (MSA-C) exhibits faster disease progression than does hereditary spinocerebellar degeneration (hSCD). In this study, we aimed to investigate the differences in the treatment effects and sustainability of intensive rehabilitation between patients with hSCD and those with MSA-C. Forty-nine patients (hSCD = 30, MSA-C = 19) underwent a 2- or 4-week intensive rehabilitation program. Balance function was evaluated using the scale for the assessment and rating of ataxia (SARA) and the balance evaluation systems test (BESTest) at pre-intervention, post-intervention, and 6-month follow-up. Notably, both groups demonstrated beneficial effects from the rehabilitation intervention. However, differences were observed in the magnitude and duration of these effects. In the hSCD group, the SARA scores at follow-up remained similar to those at baseline, indicating sustained benefits. However, the MSA-C group showed some deterioration in SARA scores compared with baseline scores but maintained improvements on the BESTest, demonstrating partial sustainability. Differences, mainly in sustainability, were observed between the hSCD and MSA-C groups. This may be due to varying rates of symptom progression. The findings of this study are significant when considering the frequency of follow-ups based on disease type.

Logistic regression analysis and machine learning for predicting post-stroke gait independence: a retrospective study.

This study investigated whether machine learning (ML) has better predictive accuracy than logistic regression analysis (LR) for gait independence at discharge in subacute stroke patients (n = 843) who could not walk independently at admission. We developed prediction models using LR and five ML algorithms-specifically, the decision tree (DT), support vector machine, artificial neural network, ensemble learning, and k-nearest neighbor methods. Functional Independence Measure sub-items were used to evaluate the ability to walk independently. Model predictive accuracies were evaluated using areas under receiver operating characteristic curves (AUCs) as well as accuracy, precision, recall, F1 score, and specificity. The AUC for DT (0.812) was significantly lower than those for the other algorithms (p < 0.01); however, the AUC for LR (0.895) did not differ significantly from those for the other models (0.893-0.903). Other performance metrics showed no substantial differences between LR and ML algorithms. In conclusion, the DT algorithm had significantly low predictive accuracy, and LR showed no significant difference in predictive accuracy compared with the other ML algorithms. As its predictive accuracy is similar to that of ML, LR can continue to be used for predicting the prognosis of gait independence, with additional advantages of being easily understandable and manually computable.

Video-Based Detection of Freezing of Gait in Daily Clinical Practice in Patients With Parkinsonism.

Freezing of gait (FoG) is a prevalent symptom among individuals with Parkinson's disease and related disorders. FoG detection from videos has been developed recently; however, the process requires using videos filmed within a controlled environment. We attempted to establish an automatic FoG detection method from videos taken in uncontrolled environments such as in daily clinical practices. Motion features of 16 patients were extracted from timed-up-and-go test in 109 video data points, through object tracking and three-dimension pose estimation. These motion features were utilized to form the FoG detection model, which combined rule-based and machine learning-based models. The rule-based model distinguished the frames in which the patient was walking from those when the patient has stopped, using the pelvic position coordinates; the machine learning-based model distinguished between FoG and stop using a combined one-dimensional convolutional neural network and long short-term memory (1dCNN-LSTM). The model achieved a high intraclass correlation coefficient of 0.75-0.94 with a manually-annotated duration of FoG and %FoG. This method is novel as it combines object tracking, 3D pose estimation, and expert-guided feature selection in the preprocessing and modeling phases, enabling FoG detection even from videos captured in uncontrolled environments.

Two-minute standing endurance test for axial postural abnormalities in patients with Parkinson's disease.

BACKGROUND: Photo-based measurement methods are used to assess axial postural abnormalities (PA) in Parkinson's disease (PD). However, they capture only moments in time. We developed the 2-minute standing endurance test (2 M-SET), which specifically captures temporal changes in posture, as a novel dynamic method for measuring axial PA in patients with PD. RESEARCH QUESTION: This study aimed to verify the effectiveness and validity of the 2 M-SET for capturing temporal changes in axial PA in patients with PD. METHODS: Twenty-eight patients with PD participated. The participants attempted to maintain an upright posture for 2 minutes during three tasks: standing, stepping in place, and walking. The rate of change in postural angle was recorded at 10-second intervals. Based on the results, the 2 M-SET was developed. Therapists evaluated the 2 M-SET using the NeuroPostureApp© to measure anterior trunk flexion (ATF) angles and lateral trunk flexion (LTF) angles at 0, 10, 30, 60, and 120 seconds. To assess reliability, the congruence between the measurements obtained by the therapists and those obtained using a three-dimensional motion-analysis system was examined. For validity, we assessed whether the ATF and LTF angles measured by the therapists could accurately capture postural changes at regular intervals over time. RESULTS: The average postural changes over 2 minutes for the standing, stepping in place, and gait tasks were 59.2±83.5%, 37.6±30.7%, and 45.4±50.6%, respectively. The intraclass correlation coefficients showed high reliability, with values of 0.985 and 0.970 for the ATF and LTF angles, respectively. SIGNIFICANCE: The results of our proposed 2 M-SET method, which uses temporal photo-based measurements to assess the patient's ability to maintain an upright standing position for 2 minutes, demonstrate the potential to capture temporal changes in axial PA. DATA AVAILABILITY STATEMENT: The data supporting the findings of this study are available upon reasonable request and approval from the local ethics committee.

Management of medial luxation of the shoulder joint in toy-breed dogs using an antiluxation pin placed lateral to the supraspinatus muscle tendon: 20 limbs (2017-2022).

OBJECTIVE: To describe the clinical and diagnostic findings, surgical procedures, and clinical course of dogs with medial shoulder luxation (MSL) treated with a novel method using an antiluxation pin. ANIMALS: 18 client-owned toy-breed dogs (20 treated limbs). CLINICAL PRESENTATION: Toy-breed dogs with MSL were treated with the antiluxation pin (2017 to 2022). The collected data included signalment, cause of luxation, preoperative and follow-up clinical evaluations with lameness scores (LMS), and radiographic and/or CT findings. RESULTS: Toy Poodle was the most represented breed (17 of 18 dogs [94.4%]). The median age was 10 years. One of 18 dogs had a history of trauma. Medial luxation was confirmed in all limbs using radiography or palpation under general anesthesia. Reluxation occurred in 3 limbs at 1, 4, and 30 days after surgery, respectively. Of these 3 limbs, 1 limb underwent revision to replace the original pin and the other 2 limbs underwent no further treatment. One limb with persistent pain underwent 2 revision surgeries to adjust the pin orientation 30 and 72 days after the initial surgery. Eighteen limbs remained unluxated after the initial or revision surgery until the final follow-up (median, 18.5 months; range, 1 to 63 months). The LMS at the final follow-up for the 18 unluxated limbs (mean, 0.5) was significantly lower than the preoperative LMS (mean, 4.5) (P < .01). CLINICAL RELEVANCE: A novel method of the antiluxation pin provides an alternative surgical treatment for MSL in toy-breed dogs that is minimally invasive and technically simple.

Validity of the Functional Classification of the Upper Extremities for Duchenne Muscular Dystrophy.

Objectives: Some upper-limb function assessments can evaluate treatments in the non-ambulatory stage of Duchenne muscular dystrophy (DMD). The Functional Classification of the Upper Extremities (FCUE) was developed for DMD in Japan. The FCUE is easier to use than the Performance of Upper Limb (PUL) and is more detailed than the Brooke Upper Extremity Scale. This study aimed to determine the concurrent validity of FCUE with other methods of assessment for DMD. Methods: This retrospective study reviewed the medical records of 39 boys with DMD from the National Center of Neurology and Psychiatry to evaluate the concurrent validity of the FCUE and PUL using non-parametric Spearman rank correlation (ρ). We also determined the concurrent validity of the Brooke Upper Extremity Scale and PUL for comparison. Results: The ρ value between the FCUE and PUL was -0.914 (P<0.001). The FCUE showed robust concurrent validity with the PUL. That correlation between the FCUE and Brooke Upper Extremity Scale gave a ρ value of -0.854 (P<0.001). Conclusions: The FCUE had a higher concurrent validity with the PUL than with the Brooke Upper Extremity Scale. The FCUE is considered a valid assessment tool of upper-limb function in boys with DMD. Selecting the best assessment method depends on the severity of the patient's condition and a balance between assessment accuracy and evaluation time.

Thoracic Vertebral Canal Stenosis and Vertebral Instability in a Young Minuet Cat.

This report describes a unique case of thoracic vertebral canal stenosis and vertebral instability in a 1 yr old Minuet cat. The cat presented with a history of chronic progressive nonambulatory paraparesis. Myelography with neutral and stress positions revealed dynamic compression at T1-4. Computed tomography and MRI revealed multiple sites of vertebral endplate osteolysis, adjacent bone sclerosis, intervertebral disk space narrowing, and spondylotic bridging within the cervical and cranial thoracic vertebral bodies and pedicles, particularly at C6-T4. The cat underwent a right-sided T1-4 hemilaminectomy and C7-T4 vertebral stabilization using positively threaded profile pins and polymethylmethacrylate. The cat fully recovered without any complication. The case highlights the potential for young cats, especially those with a chondrodysplastic condition, to develop vertebral canal stenosis and vertebral instability. The surgical treatment described herein resulted in an excellent outcome.

Risk Factors for Post-Stroke Pneumonia in a Patient Population with Subacute Stroke: A Retrospective Cohort Study.

The risk of pneumonia and death is higher in acute stroke patients with signs of pulmonary infection on chest computed tomography (CT) at admission. However, few reports have examined the incidence of pneumonia and its predictors in subacute stroke patients. The aim of this study was to examine factors related to post-stroke pneumonia in subacute stroke patients. A total of 340 subacute stroke patients were included. Univariable logistic regression analysis was performed using variables that may contribute to pneumonia, with the development of pneumonia as the dependent variable. Multivariable logistic regression analysis using the three independent variables with the lowest p-values on the univariable logistic regression analysis was also performed to calculate adjusted odds ratios. Twenty-two patients developed pneumonia during hospitalization. The univariable logistic regression analysis showed that the top three items were serum albumin (Alb), functional Oral Intake Scale (FOIS) score, and signs of pulmonary infection on chest CT at admission. Multivariable logistic regression analysis adjusted for these three items showed that the presence of signs of pulmonary infection on chest CT at admission was the independent variable (OR: 4.45; 95% CI: 1.54-12.9). When signs of pulmonary infection are seen on admission chest CT, careful follow-up is necessary because pneumonia is significantly more likely to occur during hospitalization.

Comparing the contribution of each clinical indicator in predictive models trained on 980 subacute stroke patients: a retrospective study.

Post-stroke disability affects patients' lifestyles after discharge, and it is essential to predict functional recovery early in hospitalization to allow time for appropriate decisions. Previous studies reported important clinical indicators, but only a few clinical indicators were analyzed due to insufficient numbers of cases. Although review articles can exhaustively identify many prognostic factors, it remains impossible to compare the contribution of each predictor. This study aimed to determine which clinical indicators contribute more to predicting the functional independence measure (FIM) at discharge by comparing standardized coefficients. In this study, 980 participants were enrolled to build predictive models with 32 clinical indicators, including the stroke impairment assessment set (SIAS). Trunk function had the most significant standardized coefficient of 0.221. The predictive models also identified easy FIM sub-items, SIAS, and grip strength on the unaffected side as having positive standardized coefficients. As for the predictive accuracy of this model, R2 was 0.741. This is the first report that included FIM sub-items separately in post-stroke predictive models with other clinical indicators. Trunk function and easy FIM sub-items were included in the predictive model with larger positive standardized coefficients. This predictive model may predict prognosis with high accuracy, fewer clinical indicators, and less effort to predict.

Decompressive laminectomy with vertebral stabilization allows neurologic improvement of most Pekingese dogs with thoracolumbar vertebral instability.

OBJECTIVE: To describe the diagnostic findings, surgical techniques, and outcomes of thoracolumbar vertebral instability associated with or without articular process (AP) anomalies in Pekingese dogs. ANIMALS: 11 client-owned Pekingese dogs. PROCEDURES: Medical records (2007 to 2022) were reviewed. Inclusion criteria were Pekingese dogs with thoracolumbar vertebral instability that underwent decompressive laminectomy and vertebral stabilization. Dynamic myelographic study and/or intraoperative spinal manipulation were used to diagnose vertebral instability. Data on preoperative and postoperative neurologic status, diagnostic findings, surgical techniques, and outcomes were retrieved. RESULTS: The dogs presented with paraparesis (n = 9) or paraplegia (2). Five dogs had caudal AP anomalies. Dynamic myelographic study demonstrated single (n = 7) or multiple (4) dynamic compressions with poststress spinal cord height reduction (median, 12.5%; IQR, 6.8% to 21.2%). Of the 17 dynamic compression lesions, 5 lesions were at the disc spaces with caudal AP abnormalities. All dogs had vertebral instability confirmed by intraoperative spinal manipulation and underwent hemilaminectomy and unilateral vertebral stabilization. One dog had adjacent segment vertebral instability and underwent vertebral stabilization 3 months after the initial operation. All but 1 dog showed successful outcomes at the last follow-up (median, 16 months; IQR, 3 to 32 months). CLINICAL RELEVANCE: Vertebral instability associated with or without AP abnormalities is a potential cause of thoracolumbar spinal cord injury in Pekingese dogs. Dynamic myelographic studies and/or intraoperative spinal manipulation demonstrated vertebral instability. Spinal cord decompression and vertebral stabilization are effective, resulting in neurologic improvements in most dogs.

Improvement of predictive accuracies of functional outcomes after subacute stroke inpatient rehabilitation by machine learning models.

OBJECTIVES: Stepwise linear regression (SLR) is the most common approach to predicting activities of daily living at discharge with the Functional Independence Measure (FIM) in stroke patients, but noisy nonlinear clinical data decrease the predictive accuracies of SLR. Machine learning is gaining attention in the medical field for such nonlinear data. Previous studies reported that machine learning models, regression tree (RT), ensemble learning (EL), artificial neural networks (ANNs), support vector regression (SVR), and Gaussian process regression (GPR), are robust to such data and increase predictive accuracies. This study aimed to compare the predictive accuracies of SLR and these machine learning models for FIM scores in stroke patients. METHODS: Subacute stroke patients (N = 1,046) who underwent inpatient rehabilitation participated in this study. Only patients' background characteristics and FIM scores at admission were used to build each predictive model of SLR, RT, EL, ANN, SVR, and GPR with 10-fold cross-validation. The coefficient of determination (R2) and root mean square error (RMSE) values were compared between the actual and predicted discharge FIM scores and FIM gain. RESULTS: Machine learning models (R2 of RT = 0.75, EL = 0.78, ANN = 0.81, SVR = 0.80, GPR = 0.81) outperformed SLR (0.70) to predict discharge FIM motor scores. The predictive accuracies of machine learning methods for FIM total gain (R2 of RT = 0.48, EL = 0.51, ANN = 0.50, SVR = 0.51, GPR = 0.54) were also better than of SLR (0.22). CONCLUSIONS: This study suggested that the machine learning models outperformed SLR for predicting FIM prognosis. The machine learning models used only patients' background characteristics and FIM scores at admission and more accurately predicted FIM gain than previous studies. ANN, SVR, and GPR outperformed RT and EL. GPR could have the best predictive accuracy for FIM prognosis.

Impacts of increases and decreases of drugs on rehabilitation outcomes of subacute stroke patients.

OBJECTIVE: To examine changes in drugs for subacute stroke patients and elucidate the impact of medications on rehabilitation outcomes. MATERIALS AND METHODS: A total of 295 subacute stroke patients who were admitted to the convalescent rehabilitation ward between June 2018 and May 2019 were included. Polypharmacy was defined as five or more drugs at admission. The primary outcome was the Functional Independence Measure Total score (FIM-T) at discharge. Multiple regression analysis was performed to examine the relationships between the FIM-T at discharge and drug changes or other factors. This study was conducted in two stages. The first analysis included all stroke patients, and the second analysis included only stroke patients with polypharmacy. RESULTS: On multiple regression analysis, the number of drugs at admission (ß=-0.628) was associated with FIM-T at discharge of all stroke patients. Furthermore, the number of additional drugs during hospitalization (ß=-1.964) was associated with FIM-T at discharge in the 176 stroke patients with polypharmacy. CONCLUSION: This study suggested that the number of drugs at admission and the addition of drugs during hospitalization might have a negative impact on the rehabilitation outcomes of subacute stroke patients.

Effects of the COVID-19 Pandemic on Physical Function of Community-Dwelling People with Disabilities in Japan.

In 2020, COVID-19 spread throughout the world, and international measures such as travel bans, quarantines, and increased social distancing were implemented. In Japan, the number of infected people increased, and a state of emergency was declared from 16 April to 25 May 2020. Such a change in physical activity could lead to a decline in physical function in people with disabilities. A retrospective study was conducted to determine the impact of the pandemic on the physical function of disabled persons living in the community. Data were collected at four points in time: two points before the declaration of the state of emergency was issued and two points after the declaration period had ended. Time series data of physical function at four points in time were compared for 241 people with disabilities. The mean age was 72.39 years; 157 had stroke, 59 musculoskeletal disease, and 26 other diseases. Overall, there was a long-term decrease in walking speed (p < 0.001) and a worsening of the Timed Up-and-Go (TUG) score (p < 0.001) after the period of the state of emergency. The TUG score worsened only in the group with a walking speed of 1.0 m/s or less before the state of emergency (p = 0.064), suggesting that this group was more susceptible.

Complete vaginectomy via a ventral approach with pelvic osteotomy in a cat.

A 6-year-old, intact female, domestic short-hair cat had a 3-month history of obstipation. On physical examination and diagnostic imaging, megacolon secondary to a large, intrapelvic vaginal mass was diagnosed. An ovariohysterectomy and a complete vaginectomy via a ventral midline celiotomy and bilateral pubic and ischial osteotomies were performed. This approach allowed excellent exposure of the entire genital tract necessary to excise the large vaginal mass. The mass was histologically diagnosed as a vaginal fibrous stromal polyp. Obstipation resolved 12 h after surgery. On radiographic recheck 11 d after surgery, the colon had returned to normal size. No major surgical complications were observed. This is the first case report of a complete vaginectomy via the ventral approach with a pelvic osteotomy in a cat. Furthermore, this report describes the different surgical techniques used in animals affected by a large vaginal mass and provides evidence that an aggressive surgical approach and en-bloc excision can be considered for the management of extensive intrapelvic vaginal masses in cats.

Vaginectomie complète par voie ventrale avec ostéotomie pelvienne chez une chatte. Une chatte domestique à poils courts, intacte, âgée de 6 ans, présentait des antécédents d'obstipation depuis 3 mois. À l'examen physique et à l'imagerie diagnostique, un mégacôlon secondaire à une grosse masse vaginale intra-pelvienne a été diagnostiqué. Une ovario-hystérectomie et une vaginectomie complète via une céliotomie médiane ventrale et des ostéotomies pubiennes et ischiatiques bilatérales ont été réalisées. Cette approche a permis une excellente exposition de l'ensemble du tractus génital nécessaire pour exciser la grosse masse vaginale. La masse a été histologiquement diagnostiquée comme étant un polype stromal fibreux vaginal. L'obstipation a été résolue 12 h après la chirurgie. Lors d'une nouvelle vérification radiographique 11 jours après la chirurgie, le côlon avait retrouvé sa taille normale. Aucune complication chirurgicale majeure n'a été observée. Il s'agit du premier rapport de cas d'une vaginectomie complète par voie ventrale avec ostéotomie pelvienne chez une chatte. En outre, ce rapport décrit les différentes techniques chirurgicales utilisées chez les animaux atteints d'un gros polype vaginal et fournit des preuves qu'une approche chirurgicale agressive et une excision en bloc peuvent être envisagées pour la prise en charge des masses vaginales intra-pelviennes étendues chez les chats.(Traduit par Dr Serge Messier).

Focusing on a nickel hydrocorphinoid in a protein matrix: methane generation by methyl-coenzyme M reductase with F430 cofactor and its models.

Methyl-coenzyme M reductase (MCR) containing a nickel hydrocorphinoid cofactor, F430, is an essential enzyme that catalyzes anaerobic methane generation and oxidation. The active Ni(I) species in MCR converts methyl-coenzyme M (CH3S-CoM) and coenzyme B (HS-CoB) to methane and heterodisulfide (CoM-S-S-CoB). Extensive experimental and theoretical studies focusing on the substrate-binding cavity including the F430 cofactor in MCR have suggested two principally different reaction mechanisms involving an organonickel CH3-Ni(III) species or a transient methyl radical species. In parallel with research on native MCR itself, the functionality of MCR has been investigated in the context of model complexes of F430 and recent protein-based functional models, which include a nickel complex. In the latter case, hemoproteins reconstituted with tetradehydro- and didehydrocorrinoid nickel complexes have been found to represent useful model systems that are responsible for methane generation. These efforts support the proposed mechanism of the enzymatic reaction and provide important insight into replicating the MCR-like methane-generation process. Furthermore, the modeling of MCR described here is expected to lead to understanding of protein-supported nickel porphyrinoid chemistry as well as the creation of MCR-inspired catalysis.

Dynamic mechanical interaction between injection liquid and human tissue simulant induced by needle-free injection of a highly focused microjet.

This study investigated the fluid-tissue interaction of needle-free injection by evaluating the dynamics of the cavity induced in body-tissue simulant and the resulting unsteady mechanical stress field. Temporal evolution of cavity shape, stress intensity field, and stress vector field during the injection of a conventional injection needle, a proposed highly focused microjet (tip diameter much smaller than capillary nozzle), and a typical non-focused microjet in gelatin were measured using a state-of-the-art high-speed polarization camera, at a frame rate up to 25,000 f.p.s. During the needle injection performed by an experienced nurse, high stress intensity lasted for an order of seconds (from beginning of needle penetration until end of withdrawal), which is much longer than the order of milliseconds during needle-free injections, causing more damage to the body tissue. The cavity induced by focused microjet resembled a funnel which had a narrow tip that penetrated deep into tissue simulant, exerting shear stress in low intensity which diffused through shear stress wave. Whereas the cavity induced by non-focused microjet rebounded elastically (quickly expanded into a sphere and shrank into a small cavity which remained), exerting compressive stress on tissue simulant in high stress intensity. By comparing the distribution of stress intensity, tip shape of the focused microjet contributed to a better performance than non-focused microjet with its ability to penetrate deep while only inducing stress at lower intensity. Dynamic mechanical interaction revealed in this research uncovered the importance of the jet shape for the development of minimally invasive medical devices.

Long-Term Outcome After Surgical Resection of a Spinal Choroid Plexus Tumor in a Dog.

A 6 yr old castrated male Clumber spaniel was referred for evaluation of acute paraplegia. MRI of the thoracolumbar spine demonstrated an intradural-extramedullary mass lesion at the level of T12 and extradural spinal cord compression at L1-L2. A hemilaminectomy was performed to achieve gross total resection of the mass lesion and removal of extruded disc material. A diagnosis of spinal choroid plexus tumor (CPT) and intervertebral disc extrusion was made. At 4 mo postoperatively, MRI demonstrated a mass lesion at the right lateral aperture of the fourth ventricle. Spinal drop metastasis from a primary intracranial CPT was suspected. The dog was ambulating independently and neurologically normal at that time. At 17 mo postoperatively, a third MRI was performed owing to decreased postural reactions in both hind limbs and vision loss in the right eye, and it demonstrated an increase in size of the intracranial mass lesion. These two additional MRI studies of the entire central nervous system showed no other metastatic lesions nor any evidence of local recurrence. At 25 mo postoperatively, the dog died at home. This is the first case report of surgical intervention and antemortem histopathological diagnosis of a spinal CPT in a dog.

Time-dependent oviposition deterrence by an oviposition mark in a fungus-farming lizard beetle.

In insects, the selection of a suitable oviposition site is critical for offspring performance. Avoiding hosts already occupied by conspecific immatures in oviposition is one of the mechanisms to reduce intraspecific competition. The avoidance of such hosts by ovipositing females has been well-documented in parasitoid wasps and phytophagous insects but remains unknown in mycophagous insects. Here, we report that oviposition marks (OMs) of the fungus-farming lizard beetle, Doubledaya bucculenta (Coleoptera: Erotylidae: Languriinae), deter conspecific females from oviposition. The females excavate a wall of host bamboo internodes to access cavities for oviposition and plug the holes with excised bamboo fibers after oviposition. A larva completes its development within a single internode. To determine what types of OMs function as oviposition deterrents and how the oviposition-deterring pattern associates with offspring survival, we examined the oviposition behaviors, egg-period lengths, and reactions of larvae to eggs. When a single internode was provided, most females laid eggs in internodes with no OMs, incomplete OMs, or plug-removed completed OMs (COMs), but fewer females laid in internodes with fresh COMs and no females laid in those with old COMs. When eggs were reared under constant temperatures, egg-period lengths varied, suggesting that later-laid eggs sometimes hatch earlier than earlier-laid eggs. When a larva encountered an egg, all eggs were killed shortly. These results suggest that the females avoid internodes associated with high offspring mortality and that the COM's plug contains an oviposition-deterring cue. Given that larvae of oviposition-deterring insects including D. bucculenta inhabit spatiotemporally-limited sites and have limited mobility, high resource competition in the larval stage may have driven the evolution of oviposition deterrence.

Methane Generation and Reductive Debromination of Benzylic Position by Reconstituted Myoglobin Containing Nickel Tetradehydrocorrin as a Model of Methyl-coenzyme M Reductase.

Methyl-coenzyme M reductase (MCR), which contains the nickel hydrocorphinoid cofactor F430, is responsible for biological methane generation under anaerobic conditions via a reaction mechanism which has not been completely elucidated. In this work, myoglobin reconstituted with an artificial cofactor, nickel(I) tetradehydrocorrin (NiI(TDHC)), is used as a protein-based functional model for MCR. The reconstituted protein, rMb(NiI(TDHC)), is found to react with methyl donors such as methyl p-toluenesulfonate and trimethylsulfonium iodide with methane evolution observed in aqueous media containing dithionite. Moreover, rMb(NiI(TDHC)) is found to convert benzyl bromide derivatives to reductively debrominated products without homocoupling products. The reactivity increases in the order of primary > secondary > tertiary benzylic carbons, indicating steric effects on the reaction of the nickel center with the benzylic carbon in the initial step. In addition, Hammett plots using a series of para-substituted benzyl bromides exhibit enhancement of the reactivity with introduction of electron-withdrawing substituents, as shown by the positive slope against polar substituent constants. These results suggest a nucleophilic SN2-type reaction of the Ni(I) species with the benzylic carbon to provide an organonickel species as an intermediate. The reaction in D2O buffer at pD 7.0 causes a complete isotope shift of the product by +1 mass unit, supporting our proposal that protonation of the organonickel intermediate occurs during product formation. Although the turnover numbers are limited due to inactivation of the cofactor by side reactions, the present findings will contribute to elucidating the reaction mechanism of MCR-catalyzed methane generation from activated methyl sources and dehalogenation.

Switch of tablet manufacturing from high shear granulation to twin-screw granulation using quality by design approach.

This study aimed to transfer a high shear granulation (HSG) process to a twin-screw granulation (TSG) process while maintaining equivalent dissolution profiles. Ibuprofen (IBP) was used as poorly soluble model drug. Granules were obtained by HSG or TSG according to a full factorial design. The liquid-to-solid ratio and wet massing time (HSG) or powder throughput (TSG) were selected as factors. The granules were compressed to tablets with immediate release and a drug load of 50% (w/w). Quality attributes (QAs) of the granules, especially the granule strength (GS), and the resulting tablets were evaluated. The effect of process parameters on the QAs was statistically analyzed. The comparison of HSG tablets with TSG tablets revealed that TSG tablets showed higher tensile strength and lower ejection force than HSG tablets. The dissolution profiles of the tablets in different pH media were also evaluated. Equivalent dissolution profiles in all four media (e.g., f2 values ≥ 54 in pH5.5) were obtained by adjusting process parameters. It was concluded that the GS was the most important QA for dissolution.