Identification of YigL as a PLP/PNP phosphatase in Escherichia coli.

In various organisms, the coenzyme form of vitamin B6, pyridoxal phosphate (PLP), is synthesized from pyridoxine phosphate (PNP). Control of PNP levels is crucial for metabolic homeostasis because PNP has the potential to inhibit PLP-dependent enzymes and proteins. Although the only known pathway for PNP metabolism in Escherichia coli involves oxidation by PNP oxidase, we detected a strong PNP phosphatase activity in E. coli cell lysate. To identify the unknown PNP phosphatase(s), we performed a multicopy suppressor screening using the E. coli serA pdxH strain, which displays PNP-dependent conditional lethality. The results showed that overexpression of the yigL gene, encoding a putative sugar phosphatase, effectively alleviated the PNP toxicity. Biochemical analysis revealed that YigL has strong phosphatase activity against PNP. A yigL mutant exhibited decreased PNP phosphatase activity, elevated intracellular PNP concentrations, and increased PNP sensitivity, highlighting the important role of YigL in PNP homeostasis. YigL also shows reactivity with PLP. The phosphatase activity of PLP in E. coli cell lysate was significantly reduced by mutation of yigL and nearly abolished by additional mutation of ybhA, which encodes putative PLP phosphatase. These results underscore the important contribution of YigL, in combination with YbhA, as a primary enzyme in the dephosphorylation of both PNP and PLP in E. coli.IMPORTANCEPyridoxine phosphate (PNP) metabolism is critical for both vitamin B6 homeostasis and cellular metabolism. In Escherichia coli, oxidation of PNP was the only known mechanism for controlling PNP levels. This study uncovered a novel phosphatase-mediated mechanism for PNP homeostasis. Multicopy suppressor screening, kinetic analysis of the enzyme, and knockout/overexpression studies identified YigL as a key PNP phosphatase that contributes to PNP homeostasis when facing elevated PNP concentrations in E. coli. This study also revealed a significant contribution of YigL, in combination with YbhA, to PLP metabolism, shedding light on the mechanisms of vitamin B6 regulation in bacteria.

Capturing temperature changes on the ocular surface along with estrus and ovulation using infrared thermography in Japanese Black cows.

Pre-ovulatory follicles are cooler than the neighboring reproductive organs in cows. Thus, measuring the temperature of reproductive organs could be a useful method for predicting estrus and ovulation in cows, and the establishment of a non-invasive technique is required. In this study, we used infrared thermography (IRT) to measure ocular surface temperature as a potential surrogate for reproductive organ temperature. Five Japanese Black cows with synchronized estrus were subjected to temperature measurements in five regions of the ocular surface, including the nasal conjunctiva, nasal limbus, center cornea, temporal limbus, and temporal conjunctiva, twice a day (0800 h and 1600 h) during the experimental period. The temperatures in the five regions significantly declined in cows from estrus to ovulation. To the best of our knowledge, this study is the first to use IRT to show a temperature decrease in the ocular surface along with estrus to ovulation in Japanese Black cows.

Combination Psychotropic Use for Schizophrenia With Long-Acting Injectable Antipsychotics and Oral Antipsychotics: A Nationwide Real-World Study in Japan.

BACKGROUND: Although several guidelines recommend monotherapy with antipsychotics for the treatment of schizophrenia, patients who receive long-acting injectable antipsychotics (LAIs) are frequently treated with oral antipsychotics (OAPs). In the present study, we investigated the detailed use of psychotropic medications among patients throughout Japan with schizophrenia who received LAIs or OAPs. METHODS: The present study used data from the project for the Effectiveness of Guidelines for Dissemination and Education in psychiatric treatment from 94 facilities in Japan. The LAI group included patients who received any LAI, and the non-LAI group included patients who took only OAP medications at discharge. The participants of this study were 2518 schizophrenia patients (263 in the LAI group and 2255 in the non-LAI group) who received inpatient treatment and had prescription information at discharge between 2016 and 2020. RESULTS: This study revealed significantly higher rates of polypharmacy antipsychotics, number of antipsychotics, and chlorpromazine equivalents in the LAI group than in the non-LAI group. In contrast, the LAI group showed lower rate of concomitant use of hypnotic and/or antianxiety medication than the non-LAI group. CONCLUSIONS: Presenting these real-world clinical results, we want to encourage clinicians to keep monotherapy in mind for the treatment of schizophrenia, especially by reducing concomitant use of antipsychotics in the LAI group and reducing hypnotic and/or antianxiety medication in the non-LAI group.

A Molecular Dynamics Simulation for Thermal Activation Process in Covalent Bond Dissociation of a Crosslinked Thermosetting Polymer.

A novel algorithm for covalent bond dissociation is developed to accurately predict fracture behavior of thermosetting polymers via molecular dynamics simulation. This algorithm is based on the Monte Carlo method that considers the difference in local strain and bond-dissociation energies to reproduce a thermally activated process in a covalent bond dissociation. This study demonstrates the effectiveness of this algorithm in predicting the stress-strain relationship of fully crosslinked thermosetting polymers under uniaxial tensile conditions. Our results indicate that the bond-dissociation energy plays an important role in reproducing the brittle fracture behavior of a thermosetting polymer by affecting the number of covalent bonds that are dissociated simultaneously.

Prevalence of common aneuploidy in twin pregnancies.

The incidence of chromosomal abnormalities in twin pregnancies is not well-studied. In this retrospective study, we investigated the frequency of chromosomal abnormalities in twin pregnancies and compared the incidence of chromosomal abnormalities in dichorionic diamniotic (DD) and monochorionic diamniotic (MD) twins. We used data from 57 clinical facilities across Japan. Twin pregnancies of more than 12 weeks of gestation managed between January 2016 and December 2018 were included in the study. A total of 2899 and 1908 cases of DD and MD twins, respectively, were reported, and the incidence of chromosomal abnormalities in one or both fetuses was 0.9% (25/2899) and 0.2% (4/1908) in each group (p = 0.004). In this study, the most common chromosomal abnormality was trisomy 21 (51.7% [15/29]), followed by trisomy 18 (13.8% [4/29]) and trisomy 13 (6.9% [2/29]). The incidence of trisomy 21 in MD twins was lower than that in DD twins (0.05% vs. 0.5%, p = 0.007). Trisomy 21 was less common in MD twins, even when compared with the expected incidence in singletons (0.05% vs. 0.3%, RR 0.15 [95% CI 0.04-0.68]). The risk of chromosomal abnormality decreases in twin pregnancies, especially in MD twins.

Plasticized liquid crystal networks and chemical motors for the active control of power transmission in mechanical devices.

The miniaturization of mechanical devices poses new challenges in powering, actuation, and control since traditional approaches cannot be used due to inherent size limitations. This is particularly challenging in untethered small-scale machines where independent actuation of multicomponent and multifunctional complex systems is required. This work showcases the integration of self-powered chemical motors and liquid crystal networks into a powertrain transmission device to achieve orthogonal untethered actuation for power and control. Driving gears with a protein-based chemical motor were used to power the transmission system with Marangoni propulsive forces, while photothermal liquid crystal networks were used as a photoresponsive clutch to engage/disengage the gear system. Liquid crystal networks were plasticized for optimized photothermal bending actuation to break the surface tension of water and achieve reversible immersion/resurfacing at the air-water interface. This concept is demonstrated in a milliscale transmission gear system and offers potential solutions for aquatic soft robots whose powering and control mechanisms must be necessarily decoupled.

Ultrasound guidance versus landmark method for peripheral venous cannulation in adults.

BACKGROUND: Peripheral intravenous cannulation is one of the most fundamental and common procedures in medicine. Securing a peripheral line is occasionally difficult with the landmark method. Ultrasound guidance has become a standard procedure for central venous cannulation, but its efficacy in achieving peripheral venous cannulation is unclear. OBJECTIVES: To evaluate the effectiveness and safety of ultrasound guidance compared to the landmark method for peripheral intravenous cannulation in adults.  SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 29 November 2021. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs (RCTs in which participants are systematically allocated based on data such as date of birth or recruitment) comparing the effects of ultrasound guidance to the landmark method for peripheral intravenous cannulation in adults. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were first-pass success of cannulation, overall success of cannulation, and pain. Our secondary outcomes were procedure time for first-pass cannulation, procedure time for overall cannulation, number of attempts, patient satisfaction, and overall complications. We used GRADE to assess the certainty of the evidence.  Placing a peripheral intravenous line in individuals can be classed as 'difficult', 'moderate', or 'easy'. We use the terms 'difficult participants', 'moderate/moderately difficult participants' and 'easy participants' as shorthand to characterise the difficulty level in placing a peripheral line using the landmark method. We used the original studies' definitions of difficulty levels of peripheral intravenous cannulation with the landmark method. We analysed the results in these subgroups: 'difficult participants', 'moderate participants', and 'easy participants'. We did this because we expected the effect of ultrasound-guided peripheral venous cannulation to be largest in participants classed as 'difficult' and smaller in participants classed as 'moderate' and 'easy'.  MAIN RESULTS: We included 14 RCTs and two quasi-RCTs involving 2267 participants undergoing peripheral intravenous cannulation. Participants were classed as 'difficult' in 12 studies (880 participants), 'moderate' in one study (401 participants), and 'easy' in one study (596 participants). Two studies (390 participants) did not restrict by landmark method difficulty level. The overall risk of bias assessments ranged from low to high. We judged studies to be at high risk of bias mainly because of concerns about blinding for subjective outcomes. In difficult participants, ultrasound guidance increased the first-pass success of cannulation (risk ratio (RR) 1.50, 95% confidence interval (95% CI) 1.15 to 1.95; 10 studies, 815 participants; low-certainty evidence), and the overall success of cannulation (RR 1.40, 95% CI 1.10 to 1.77; 10 studies, 670 participants; very low-certainty evidence). There was no clear difference in pain (mean difference (MD) -0.20, 95% CI -1.13 to 0.72; 4 studies, 323 participants; very low-certainty evidence; numerical rating scale (NRS) 0 to 10 where 10 is maximum pain). Ultrasound guidance increased the procedure time for first-pass cannulation (MD 119.9 seconds, 95% CI 88.6 to 151.1; 2 studies, 219 participants; low-certainty evidence), and patient satisfaction (standardised mean difference (SMD) 0.49, 95% CI 0.07 to 0.92; 5 studies, 333 participants; very low-certainty evidence; NRS 0 to 10 where 10 is maximum satisfaction). Ultrasound guidance decreased the number of cannulation attempts (MD -0.33, 95% CI -0.64 to -0.02; 9 studies, 568 participants; very low-certainty evidence). Ultrasound guidance showed no clear difference in the procedure time for overall cannulation (MD -24.9 seconds, 95% CI -323.1 to 273.3; 8 studies, 413 participants; very low-certainty evidence) and overall complications (RR 0.64, 95% CI 0.37 to 1.10; 5 studies, 431 participants; low-certainty evidence).  In moderate participants, ultrasound guidance increased the first-pass success of cannulation (RR 1.14, 95% CI 1.02 to 1.27; 1 study, 401 participants; moderate-certainty evidence). No studies assessed the overall success of cannulation. There was no clear difference in pain (MD 0.10, 95% CI -0.47 to 0.67; 1 study, 401 participants; low-certainty evidence; NRS 0 to 10 where 10 is maximum pain). Ultrasound guidance increased the procedure time for first-pass cannulation (MD 95.2 seconds, 95% CI 72.8 to 117.6; 1 study, 401 participants; high-certainty evidence). Ultrasound guidance showed no clear difference in overall complications (RR 0.83, 95% CI 0.38 to 1.82; 1 study, 401 participants; moderate-certainty evidence). No studies assessed the procedure time for overall cannulation, number of cannulation attempts, or patient satisfaction.  In easy participants, ultrasound guidance decreased the first-pass success of cannulation (RR 0.89, 95% CI 0.85 to 0.94; 1 study, 596 participants; high-certainty evidence). No studies assessed the overall success of cannulation. Ultrasound guidance increased pain (MD 0.60, 95% CI 0.17 to 1.03; 1 study, 596 participants; moderate-certainty evidence; NRS 0 to 10 where 10 is maximum pain). Ultrasound guidance increased the procedure time for first-pass cannulation (MD 94.8 seconds, 95% CI 81.2 to 108.5; 1 study, 596 participants; high-certainty evidence). Ultrasound guidance showed no clear difference in overall complications (RR 2.48, 95% CI 0.90 to 6.87; 1 study, 596 participants; moderate-certainty evidence). No studies assessed the procedure time for overall cannulation, number of cannulation attempts, or patient satisfaction.  AUTHORS' CONCLUSIONS: There is very low- and low-certainty evidence that, compared to the landmark method, ultrasound guidance may benefit difficult participants for increased first-pass and overall success of cannulation, with no difference detected in pain. There is moderate- and low-certainty evidence that, compared to the landmark method, ultrasound guidance may benefit moderately difficult participants due to a small increased first-pass success of cannulation with no difference detected in pain. There is moderate- and high-certainty evidence that, compared to the landmark method, ultrasound guidance does not benefit easy participants: ultrasound guidance decreased the first-pass success of cannulation with no difference detected in overall success of cannulation and increased pain.

Generation of Caco-2 cells stably expressing CYP3A4·POR·UGT1A1 and CYP3A4·POR·UGT1A1*6 using a PITCh system.

The small intestine plays a critical role in the absorption and metabolism of orally administered drugs. Therefore, a model capable of evaluating drug absorption and metabolism in the small intestine would be useful for drug discovery. Patients with genotype UGT1A1*6 (exon 1, 211G > A) treated with the antineoplastic drug SN-38 have been reported to exhibit decreased glucuronide conjugation and increased incidence of intestinal toxicity and its severe side effects, including severe diarrhea. To ensure the safety of drugs, we must develop a drug metabolism and toxicity evaluation model which considers UGT1A1*6. In this study, we generated CYP3A4·POR·UGT1A1 KI- and CYP3A4·POR·UGT1A1*6 KI-Caco-2 cells for pharmaceutical research using a PITCh system. The CYP3A4·POR·UGT1A1 KI-Caco-2 cells were shown to express functional CYP3A4 and UGT1A1. The CYP3A4·POR·UGT1A1*6 KI-Caco-2 cells were sensitive to SN-38-induced intestinal toxicity. We thus succeeded in generating CYP3A4·POR·UGT1A1 KI- and CYP3A4·POR·UGT1A1*6 KI-Caco-2 cells, which can be used in pharmaceutical research. We also developed an intestinal epithelial cell model of patients with UGT1A1*6 and showed that it was useful as a tool for drug discovery.

Use of oral third generation cephalosporins and quinolones and occurrence of antibiotic-resistant strains in the neurogenic bladder (NB) outpatient setting: a retrospective chart audit.

STUDY DESIGN: A retrospective chart audit. OBJECTIVES: Neurogenic bladder (NB), a risk factor for urinary tract infection, has not been comprehensively studied in terms of antimicrobial stewardship. In this study, we studied the relationship between the use of oral third generation cephalosporins and quinolones, and the occurrence of antibiotic-resistant strains. SETTING: Hyogo Prefectural Central Rehabilitation Hospital, Hyogo, Japan. METHODS: We retrospectively investigated antibiotic-resistant bacteria and the amount of antibiotics prescribed in outpatients with NB caused by spinal cord injury between 2012 and 2017. We intervened in urological departments whose physicians often prescribed third generation cephalosporins and fluoroquinolone, and analyzed the number of prescriptions and the amount of Cefdinir (CFDN) and Levofloxacin (LVFX), and studied changes of ratios in antibiotic-resistant strains such as extended-spectrum ß-lactamases (ESBLs) and quinolone-resistant Escherichia coli and Klebsiella pneumoniae. RESULTS: The number of CFDN prescriptions per year significantly decreased from 463 cases to 130 cases over 6 years (p = 0.012). The number of LVFX prescriptions per year decreased from 640 cases to 171 cases (p = 0.025). The incidence rate of ESBL-producing K. pneumoniae decreased from 25% to 7% of total K. pneumoniae (p < 0.001). The incidence of LVFX-resistant E. coli and K. pneumoniae significantly decreased in 2017 compared with 2012 (p = 0.03 and p = 0.016, respectively). CONCLUSIONS: Antimicrobial stewardship interventions decreased the use of CFDN and LVFX for outpatients with NB. Our findings suggested that the reduction in the use of third generation cephalosporins and quinolones correlates with observed decrease in the occurrence of antibiotic-resistant, ESBL-producing, and quinolone-resistant bacteria.

MRI evaluation of motor function recovery by rTMS and intensive occupational therapy and changes in the activity of motor cortex.

Purpose/aim: An intervention that combines low-frequency repetitive transcranial magnetic stimulation and intensive occupational therapy can improve brain function in post-stroke patients with motor paralysis. The purpose of the present study is examined motor function recovery by repetitive transcranial magnetic stimulation and intensive occupational therapy and changes in the activity of motor cortex based on magnetic resonance imaging data.Materials and methods: In total, we assessed 30 patients with post-stroke upper extremity paralysis who were hospitalized for 12 sessions of low-frequency repetitive transcranial magnetic stimulation over the lesion-free hemisphere plus daily occupational therapy for 15 days. Imaging analysis was performed using 3-dimensional T1-weighted image and functional magnetic resonance imaging. Hemispheric dominance was assessed by functional magnetic resonance imaging using the laterality index. In addition, Seed-based functional connectivity analysis was used to evaluate functional connectivity between the precentral gyrus of the affected side and other areas.Results: A positive correlation was found between laterality index before intervention and the Brunnstrom recovery stage for hand/fingers (p < 0.05). The intervention resulted in significantly higher functional connectivity between the precentral gyrus of the affected side and that of the healthy side (false discovery rate corrected p < 0.05).Conclusions: We clarified that the recovery of motor function by intervention with low-frequency repetitive transcranial magnetic stimulation and occupational therapy and the increase of functional connectivity between the precentral gyrus on the affected side and the healthy side are related. These results facilitate prognostic predictions and evidence-based medical care.

The 2-Minute Spontaneous Swallowing Screening Predicts Independence on Enteral Feeding in Patients with Acute Stroke.

BACKGROUND: It is recommended that enteral feeding should be offered to patients with dysphagia estimated to be unable to take adequate diet orally within 7 days of admission after acute stroke, but there is no clear criterion for initiation of enteral feeding. Recent studies have reported that the frequency of spontaneous swallowing is useful in screening for dysphagia in acute stroke. The present study was aimed to investigate whether measurement of frequency of spontaneous swallowing for 2 minutes could predict independence on enteral feeding 1 week after admission in patients with acute stroke. METHODS: Patients with acute stroke were subjected. Within 72 hours of stroke onset, the number of swallows for 2 minutes was measured by auscultation. Subsequently, 1-hour frequency of spontaneous swallowing was measured using a laryngeal microphone. Functional Oral Intake Scale (FOIS) was evaluated 1 week after admission. RESULTS: Twenty-six out of 40 patients were independent on enteral feeding 1 week after admission based on FOIS. The presence of spontaneous swallowing for 2 minutes had .89 sensitivity, .54 specificity to predict independence on enteral feeding 1 week after admission, whereas the 1-hour frequency of spontaneous swallowing had 1.00 sensitivity, .46 specificity. Logistic regression analysis demonstrated that the presence of spontaneous swallowing for 2 minutes was independent predictor for independence on enteral feeding 1 week after admission, independently of age, sex, and NIHSS. CONCLUSIONS: The 2-minute spontaneous swallowing screening predicts independence on enteral feeding 1 week after admission in patients with acute stroke.

Role of D-serine in the beneficial effects of repetitive transcranial magnetic stimulation in post-stroke patients.

OBJECTIVE: Abnormalities in neurotransmission via N-methyl-D-aspartic acid receptor (NMDAR) play a role in the pathophysiology of neuropsychiatric disorders. The impact of repetitive transcranial magnetic stimulation (rTMS) on NMDAR-related amino acids remains unknown. We aim to investigate the effects of rTMS on NMDAR-related amino acids in serum of post-stroke patients. METHODS: Ninety-five consecutive post-stroke patients with upper limb hemiparesis were recruited. In 27 patients, the Beck Depression Inventory (BDI) score was 10 or higher. Twelve depressed patients underwent rehabilitation in combination with rTMS and 15 non-depressed patients underwent rehabilitation only without rTMS for 14 days. 1 Hz rTMS was applied to the primary motor area in the non-lesional hemisphere. BDI was conducted before and after treatment. Serum glutamine, glutamate, glycine, L-serine, and D-serine levels were measured before and after treatment. RESULTS: There were no differences between depressed patients and non-depressed patients in clinical characteristics, levels of the five amino acids in serum, and the ratio of amino acids. However, in 27 depressed patients there was a significant correlation between levels of glutamate in serum and BDI (ρ=0.428、p=0.026). BDI decreased significantly in depressed patients after treatment with or without rTMS. D-serine decreased in the rehabilitation with rTMS group, but increased in the rehabilitation without rTMS group. L-serine increased in the rehabilitation with rTMS group, but decreased in the rehabilitation without rTMS group. CONCLUSIONS: The results suggest that rTMS can modulate NMDAR-related amino acids in blood, producing beneficial effects.

Type A aortic dissection associated with tension pneumothorax.

Both aortic dissection and tension pneumothorax are conditions that require urgent treatments. However, the diagnosis of these emergencies is sometimes challenging because of various symptoms and difficulty obtaining their medical history due to severe conditions. Here, we present the case of a patient with type A aortic dissection associated with tension pneumothorax. This is the second report of such a case worldwide. A 61-year-old man presented to the emergency department with sudden-onset chest and back pain. Upon presentation, his blood pressure was 97/58 mmHg, oxygen saturation on room air was 96%, and respiratory rate was 28 breaths/min. His physical examination revealed no jugular venous distention; however, breath sounds over the left lung were diminished. Bedside chest radiography revealed left tension pneumothorax with mediastinal shift to the right. Needle and chest tube thoracostomies were performed; however, the patient's vital signs did not improve and reexpansion pulmonary edema developed following tube thoracostomy. Contrast-enhanced computed tomography revealed type A thrombosed aortic dissection with bullae in the upper lobe of the left lung. Therefore, the patient was admitted to the intensive care unit, conservatively treated, and discharged without any complications. In conclusion, type A aortic dissection may be associated with tension pneumothorax and should be considered if the patient's vital signs do not improve even after decompression of the tension pneumothorax.

Diffusion Tensor Imaging Evaluation of Neural Network Development in Patients Undergoing Therapeutic Repetitive Transcranial Magnetic Stimulation following Stroke.

We aimed to investigate plastic changes in cerebral white matter structures using diffusion tensor imaging following a 15-day stroke rehabilitation program. We compared the detection of cerebral plasticity between generalized fractional anisotropy (GFA), a novel tool for investigating white matter structures, and fractional anisotropy (FA). Low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) of 2400 pulses applied to the nonlesional hemisphere and 240 min intensive occupation therapy (OT) daily over 15 days. Motor function was evaluated using the Fugl-Meyer assessment (FMA) and Wolf Motor Function Test (WMFT). Patients underwent diffusion tensor magnetic resonance imaging (MRI) on admission and discharge, from which bilateral FA and GFA values in Brodmann area (BA) 4 and BA6 were calculated. Motor function improved following treatment (p < 0.001). Treatment increased GFA values for both the lesioned and nonlesioned BA4 (p < 0.05, p < 0.001, resp.). Changes in GFA value for BA4 of the lesioned hemisphere were significantly inversely correlated with changes in WMFT scores (R2 = 0.363, p < 0.05). Our findings indicate that the GFA may have a potentially more useful ability than FA to detect changes in white matter structures in areas of fiber intersection for any such future investigations.

Relationship Between Frequency of Spontaneous Swallowing and Salivary Substance P Level in Patients with Acute Stroke.

The frequency of spontaneous swallowing is useful for screening of dysphagia in acute stroke. Low levels of substance P (SP) in saliva attenuate the swallowing reflex. The aim of this study was to determine the relationship between the frequency of spontaneous swallowing and salivary SP levels. In 40 subjects, saliva was collected within 72 h after stroke onset and salivary SP levels were measured using ELISA kit at a later date. The frequency of spontaneous swallowing was measured over 1 h using a microphone placed on the neck. Pneumonia was diagnosed by the presence of pyrexia and at least two respiratory problems of four categories (sputum, cough or breathing pattern, breath sound, and gas change). The presence of detectable levels of SP in the saliva was confirmed in 17 patients (high SP group), whereas the level was below the detection limit of the ELISA kit in 23 patients (low SP group). The frequency of spontaneous swallowing was significantly lower in low SP group (16.1 ± 11.6 per hour) than in the high SP group (30.4 ± 20.4, p = 0.016). As the result of multiple regression analysis, salivary SP levels were correlated with frequency of spontaneous swallowing independently of age, NIHSS, and GCS. The incidence of pneumonia was significantly higher in the low than high SP group (p < 0.001). In conclusion, the frequency of spontaneous swallowing was decreased in acute stroke patients with low salivary SP levels. Salivary SP levels can be potentially a useful biomarker of risk of stroke-associated pneumonia in the acute stage.

Occurrence and characterization of carbapenem-resistant Gram-negative bacilli: A collaborative study of antibiotic-resistant bacteria between Indonesia and Japan.

OBJECTIVES: To explore the occurrence and characterization of carbapenemase-producing pathogens among carbapenem-resistant Gram-negative bacilli isolated from hospitalized patients with urinary tract infection in Indonesia. METHODS: This was a study promoted by the Japanese-Indonesian collaborative research program in the Japan Initiative for Global Research Network on Infectious Diseases. Bacterial pathogens were prospectively isolated from urine specimens of hospitalized urinary tract infection patients at Dr. Soetomo Hospital (Surabaya, Indonesia). All Gram-negative bacteria resistant to third-generation cephalosporin or carbapenem were included in this study. Carbapenemase genes were investigated for phenotype and genotype. RESULTS: In total, 1082 Gram-negative bacilli were isolated, of which 116 strains were resistant to imipenem or meropenem (carbapenem-resistant Gram-negative bacilli), and 22 strains were carbapenemase-producing Gram-negative bacilli. Carbapenemase-producing Gram-negative bacilli consisted of Acinetobacter baumannii (n = 4), Pseudomonas aeruginosa (n = 4), Klebsiella pneumoniae (n = 5), Providencia rettgeri (n = 4) and five others. The carbapenemase-producing Gram-negative bacilli included NDM-1 (n = 18, 81.8%, in Enterobacteriaceae and Acinetobacter spp.) and IMP-7 (n = 4, 18.2%, all in P. aeruginosa). Among carbapenem-resistant Gram-negative bacilli, all four P. aeruginosa were sensitive to colistin, and all six Acinetobacter spp. were sensitive to minocycline, colistin and tigecycline. Of those patients harboring carbapenemase-producing Gram-negative bacilli, 12 (54.5%) were seriously ill at the time of admission, with longer hospital stays and three deaths (13.6% mortality rate). CONCLUSIONS: Urinary tract infection-causing carbapenem-resistant Gram-negative bacilli are widely disseminated in Indonesia. The NDM-1 phenotype seems to be dominant, and it can be treated with colistin and tigecycline in most cases. Most patients harboring carbapenemase-producing Gram-negative bacilli are seriously ill, have a bad prognosis, with a longer hospital stay and a significant mortality rate.

Effects of botulinum toxin A therapy and multidisciplinary rehabilitation on lower limb spasticity classified by spastic muscle echo intensity in post-stroke patients.

OBJECTIVES: The purpose of the present study was to investigate retrospectively the relationship between botulinum toxin type A plus multidisciplinary rehabilitation and muscle echo intensity in post-stroke patients with spasticity. The primary aim was to investigate whether the effects of the intervention on the improvement of spasticity depend on muscle echo intensity, and the secondary aim was to investigate whether the motor function of the lower limbs depends on muscle echo intensity. METHODS: A 12-day inpatient protocol was designed for 102 post-stroke patients with spasticity due to lower limb paralysis. Muscle echo intensity of the triceps surae muscle was measured by ultrasonography, and the patients were categorized into four groups based on Heckmatt scale grades (Grades I-IV). RESULTS: All four groups classified by the Heckmatt scale showed significant pre-to-post-intervention differences in the knee and ankle modified Ashworth scale scores (p < 0.05). Grades I-III patient groups showed a significant improvement in lower limb motor function following intervention. Grade IV patients did not show a significant improvement in lower limb motor function. CONCLUSIONS: We observed significant improvements in the modified Ashworth scale scores after botulinum toxin type A and multidisciplinary rehabilitation therapy on post-stroke patients with spasticity. Although patients with lower muscle echo intensity demonstrated improvements in motor function, the improvement was poor in those with higher muscle echo intensity.

Repetitive peripheral magnetic stimulation for activities of daily living and functional ability in people after stroke.

BACKGROUND: Repetitive peripheral magnetic stimulation (rPMS) is a form of therapy that creates painless stimulation of deep muscle structures to improve motor function in people with physical impairment from brain or nerve disorders. Use of rPMS for people after stroke has been identified as a feasible approach to improve activities of daily living and functional ability. However, no systematic reviews have assessed the findings of available trials. The effect and safety of this intervention for people after stroke currently remain uncertain. OBJECTIVES: To assess the effect of rPMS for improving activities of daily living and functional ability in people after stroke. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (August 2016), the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 8) in the Cochrane Library (August 2016), MEDLINE Ovid (November 2016), Embase Ovid (August 2016), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) in Ebsco (August 2016), PsycINFO Ovid (August 2016), the Allied and Complementary Medicine Database (AMED) Ovid (August 2016), Occupational Therapy Systematic Evaluation of Evidence (OTseeker) (August 2016), the Physiotherapy Evidence Database (PEDro) (October 2016), and ICHUSHI Web (October 2016). We also searched five ongoing trial registries, screened reference lists, and contacted experts in the field. We placed no restrictions on the language or date of publication when searching the electronic databases. SELECTION CRITERIA: We included randomised controlled trials (RCTs) conducted to assess the therapeutic effect of rPMS for people after stroke. Comparisons eligible for inclusion were (1) active rPMS only compared with 'sham' rPMS (a very weak form of stimulation or a sound only); (2) active rPMS only compared with no intervention; (3) active rPMS plus rehabilitation compared with sham rPMS plus rehabilitation; and (4) active rPMS plus rehabilitation compared with rehabilitation only. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion. The same review authors assessed methods and risk of bias and extracted data. We contacted trial authors to ask for unpublished information if necessary. We resolved all disagreements through discussion. MAIN RESULTS: We included three trials (two RCTs and one cross-over trial) involving 121 participants. Blinding of participants and physicians was well reported in all trials, and overall risk of bias was low. We found no clear effect of rPMS on activities of daily living at the end of treatment (mean difference (MD) -3.00, 95% confidence interval (CI) -16.35 to 10.35; low-quality evidence) and at the end of follow-up (MD -2.00, 95% CI -14.86 to 10.86; low-quality evidence). Investigators in one study with 63 participants observed no statistical difference in improvement of upper limb function at the end of treatment (MD 2.00, 95% CI -4.91 to 8.91) and at the end of follow-up (MD 4.00, 95% CI -2.92 to 10.92). One trial with 18 participants showed that rPMS treatment was not associated with improved muscle strength at the end of treatment (MD 3.00, 95% CI -2.44 to 8.44). Another study reported a significant decrease in spasticity of the elbow at the end of follow-up (MD -0.48, 95% CI -0.93 to -0.03). No studies provided information on lower limb function and death. Based on the GRADE approach, we judged the certainty of evidence related to the primary outcome as low owing to the small sample size of one study. AUTHORS' CONCLUSIONS: Available trials provided inadequate evidence to permit any conclusions about routine use of rPMS for people after stroke. Additional trials with large sample sizes are needed to determine an appropriate rPMS protocol as well as long-term effects. We identified three ongoing trials and will include these trials in the next review update.

The Efficacy of High-Frequency Repetitive Transcranial Magnetic Stimulation for Improving Apathy in Chronic Stroke Patients.

Although repetitive transcranial magnetic stimulation (rTMS) for hemiparesis is beneficial, so far no study has examined the usefulness of rTMS for apathy. Thirteen patients with chronic stroke were assigned randomly to 2 groups: rTMS group (n = 7) and sham stimulation group (n = 6). The patients received 5 sessions of either high-frequency rTMS over the region spanning from the dorsal anterior cingulate cortex (dACC) to medial prefrontal cortex (mPFC) or sham stimulation for 5 days. The severity of apathy was evaluated using the Apathy Scale (AS) and the severity of depression was evaluated using the Quick Inventory of Depressive Symptomatology (QIDS) serially before and after the 5-day protocol. The AS and QIDS scores were significantly improved in the rTMS group, although they were not changed in the sham stimulation group. The degree of change in the AS score was significantly greater in the rTMS group than that in the sham stimulation group. The degree of change in the QIDS score was greater in the rTMS group than that in the sham stimulation group, although the difference was not statistically significant. The application of high frequency rTMS over the dACC and mPFC may be a useful intervention for apathy due to stroke.