Integer-locking condition for stable dual-comb interferometry in situations with fluctuating frequency-comb repetition rates.

To make dual-comb interferometry usable in a wide range of applications, it is important to achieve reproducible measurement results even in non-ideal environments that affect the repetition-rate stability. Here, we consider dual-comb interferometry based on a pair of fully referenced optical frequency combs (OFCs) and investigate the impact of fluctuations in the OFC repetition frequencies on the peak position of the center burst in the interferogram. We identify a phase-locking scheme that minimizes the impact of these fluctuations through choosing a special combination of phase-locked frequencies, and the resulting type of operating condition is termed integer-locking condition. Under the integer-locking condition, the number of sampling points in each interferogram remains constant regardless of repetition-rate variations, and this enables more stable phase-resolved measurements in non-ideal environments. We demonstrate the application of this approach using absolute path-length measurements and discuss the accuracy limit imposed by the integer-locking condition. Our findings offer a strategy for robust dual-comb interferometry outside metrology laboratories.

Pharmacological Investigation of Hypoalbuminemia on the Prolonged and Potentiated Action of Midazolam in Rats.

Midazolam (MDZ) is clinically used for its sedative and anticonvulsant properties. However, its prolonged or potentiated effects are sometimes concerning. The main binding protein of MDZ is albumin, and reduced serum albumin levels could lead to MDZ accumulation, thereby potentiating or prolonging its effects. Previous investigations have not thoroughly examined these phenomena from a behavioral pharmacology standpoint. Consequently, this study aimed to evaluate both the prolonged and potentiated effects of MDZ, as well as the effects of serum albumin levels on the action of MDZ in low-albumin rats. Male Wistar rats were classified into control (20% protein diet), low-protein (5% protein), and non-protein groups (0% protein diet) and were fed the protein-controlled diets for 30 d to obtain low-albumin rats. The locomotor activity and muscle relaxant effects of MDZ were evaluated using the rotarod, grip strength, and open-field tests conducted 10, 60, and 120 min after MDZ administration. Serum albumin levels decreased significantly in the low-protein and non-protein diet groups compared with those in the control group. Compared with the control rats, low-albumin rats demonstrated a significantly shorter time to fall, decreased muscle strength, and a significant decrease in the distance traveled after MDZ administration in the rotarod, grip strength, and open-field tests, respectively. Decreased serum albumin levels potentiated and prolonged the effects of MDZ. Hence, serum albumin level is a critical parameter associated with MDZ administration, which should be monitored, and any side effects related to decreased albumin levels should be investigated.

The inter-laboratory validation study of EpiSensA for predicting skin sensitization potential.

The Epidermal Sensitization Assay (EpiSensA) is a reconstructed human epidermis (RhE)-based gene expression assay for predicting the skin sensitization potential of chemicals. Since the RhE model is covered by a stratified stratum corneum, various kinds of test chemicals, including lipophilic ones and pre-/pro-haptens, can be tested with a route of exposure akin to an in vivo assay and human exposure. This article presents the results of a formally managed validation study of the EpiSensA that was carried out by three participating laboratories. The purpose of this validation study was to assess transferability of the EpiSensA to new laboratories along with its within- (WLR) and between-laboratory reproducibility (BLR). The validation study was organized into two independent stages. As demonstrated during the first stage, where three sensitizers and one non-sensitizer were correctly predicted by all participating laboratories, the EpiSensA was successfully transferred to all three participating laboratories. For Phase I of the second stage, each participating laboratory performed three experiments with an identical set of 15 coded test chemicals resulting in WLR of 93.3%, 93.3%, and 86.7%, respectively. Furthermore, when the results from the 15 test chemicals were combined with those of the additional 12 chemicals tested in Phase II of the second stage, the BLR for 27 test chemicals was 88.9%. Moreover, the predictive capacity among the three laboratories showed 92.6% sensitivity, 63.0% specificity, 82.7% accuracy, and 77.8% balanced accuracy based on murine local lymph node assay (LLNA) results. Overall, this validation study concluded that EpiSensA is easily transferable and sufficiently robust for assessing the skin sensitization potential of chemicals.

Dysphagia Rehabilitation in Dysphagic Patients with Acute or Critical Illness: A Systematic Review and Meta-Analysis.

Dysphagia or swallowing dysfunction is common in patients with acute or critical illness, and diverse methods of dysphagia rehabilitation are provided worldwide. We aimed to examine the efficacy of rehabilitation to treat dysphagia in patients with acute or critical illness. We searched PubMed, ICHUSHI, and Cochrane Central Register of Controlled Trials databases from inception to November 22, 2023 for relevant randomized controlled trials. We focused on dysphagic patients with acute or critical illness who were not orotracheally intubated. Our target intervention included conventional rehabilitation and nerve stimulation/neuromodulation techniques as dysphagia rehabilitation. Comparators were conventional or standard care or no dysphagia interventions. Primary outcomes included mortality, incidence of pneumonia during the study period, and health-related quality of life (HRQoL) scores within 90 days of hospital discharge. We pooled the data using a random-effects model, and classified the certainty of evidence based on the Grading of Recommendations, Assessment, Development, and Evaluation system. Nineteen randomized controlled trials involving 1,096 participants were included. Dysphagia rehabilitation was associated with a reduced incidence of pneumonia (risk ratio [RR], 0.66; 95% confidence interval [CI], 0.54-0.81; moderate certainty), but not with reduced mortality (RR, 0.92; 95% CI, 0.61-1.39; very low certainty) or improved HRQoL scores (mean difference, -0.20; 95% CI, -20.34 to 19.94; very low certainty). Based on the available moderate- or very low- quality evidence, while dysphagia rehabilitation had no impact on mortality or HRQoL, they might reduce the incidence of pneumonia in dysphagic patients with acute or critical illness.

Effect of Neuromuscular Electrical Stimulation in Patients With Critical Illness: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: Neuromuscular electrical stimulation (NMES) is used in the rehabilitation of patients with critical illness. However, it is unclear whether NMES prevents ICU-acquired weakness (ICU-AW). For this purpose, we conducted an updated systematic review and meta-analysis. DATA SOURCES: We searched the MEDLINE, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi databases from April 2019 to November 2022 to identify new randomized controlled trials to the previous meta-analysis. STUDY SELECTION: We systematically searched the literature for all randomized controlled trials on the effect of NMES in patients with critical illness. DATA EXTRACTION: Two authors independently selected the studies and extracted data. They calculated the pooled effect estimates associated with the occurrence of ICU-AW and adverse events as primary outcomes and muscle mass change, muscle strength, length of ICU stay, mortality, and quality of life as secondary outcomes. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. DATA SYNTHESIS: Overall, eight studies were added to the previous 10 studies. Evidence suggests that the use of NMES reduces the occurrence of ICU-AW (six trials; risk ratio [RR], 0.48; 95% CI, 0.32-0.72); however, NMES may have little to no effect on pricking sensation in patients (eight trials; RR, 6.87; 95% CI, 0.84-56.50). NMES is likely to reduce the change in muscle mass (four trials; mean difference, -10.01; 95% CI, -15.54 to -4.48) and may increase muscle strength (six trials; standardized mean difference, 0.43; 95% CI, 0.19-0.68). Further, NMES may result in little to no difference in the length of ICU stay, and the evidence is uncertain about the effect on mortality and quality of life. CONCLUSIONS: This updated meta-analysis revealed that the use of NMES may result in a lower occurrence of ICU-AW in patients with critical illness, but its use may have little to no effect on pricking sensation in patients.

Hospital pharmacist interventions for the management of oral mucositis in patients with head and neck cancer receiving chemoradiotherapy: a multicenter, prospective cohort study.

PURPOSE: Oral mucositis is a severe adverse event in patients with head and neck cancer (HNC) receiving chemotherapy and radiotherapy that may cause the termination of cancer treatment. In this study, we aimed to reveal the benefits of pharmacist interventions in oral health care for patients with HNC receiving concurrent chemoradiotherapy (CCRT). METHODS: We conducted a multicenter, prospective cohort study on 173 patients from September 2019 to August 2022. We evaluated the association between the occurrence of oral mucositis during CCRT and various factors in the absence or presence of direct medication instructions from hospital pharmacists. RESULTS: Sixty-eight patients received medication instructions from pharmacists (the pharmacist intervention group), whereas 105 patients did not receive instructions (the control group). Logistic regression analysis showed that grade 2 (Gr 2) oral mucositis was significantly lower in patients receiving pharmacist interventions than in patients in the control group (adjusted odds ratio [aOR], 0.42; 95% confidence interval [CI], 0.18-0.96; P = 0.04). The time to onset of Gr 2 oral mucositis was significantly longer in the pharmacist intervention group than in the control group (hazard ratio, 0.53; 95% CI, 0.29-0.97; P = 0.04). CONCLUSION: Direct intervention, especially when provided by hospital pharmacists, can have a real effect in supporting patients with HNC experiencing severe side effects of treatments. Moreover, the integration of pharmacists into the oral healthcare team is becoming even more essential to reduce the severity of side effects.

The second nationwide surveillance of antibacterial susceptibility patterns of pathogens isolated from skin and soft-tissue infections in dermatology departments in Japan.

The present study compared trends in antimicrobial resistance patterns in pathogens isolated from skin and soft-tissue infections (SSTIs) in Japan with those of a nationwide survey conducted in 2013. Three organisms that caused most of the SSTIs were collected from 12 dermatology departments in medical centers and 12 dermatology clinics across Japan between April 2019 and August 2020. A total of 390 strains, including 267 Staphylococcus aureus, 109 coagulase-negative staphylococci (CNS), and 14 Streptococcus pyogenes strains were submitted to a central laboratory for antimicrobial susceptibility testing. Patient demographic and clinical information was collated. Methicillin-resistant S. aureus (MRSA) was detected in 25.8% (69/267) of the S. aureus strains. The prevalence of MRSA between the present study and the 2013 survey did not differ significantly. Furthermore, there were no significant differences in MIC values and susceptibility patterns of the MRSA strains to other agents, regardless of a history of hospitalization within 1 year or invasive medical procedures. Methicillin-resistant CNS (MRCNS) was detected in 48.6% (53/109) of CNS isolates, higher than the 35.4% prevalence in the 2013 survey. This difference could be attributed to the heterogeneity in the members of the MRCNS, which comprises multiple staphylococci species, between the 2013 and 2019 surveys. However, it was noted that the susceptibility profiles of the MRCNS to each antibiotic were not significantly different from those identified in the 2013 survey. Most strains of S. pyogenes were susceptible to each antibiotic, similar to the 2013 survey. Continuous monitoring of trends in pathogen and susceptibility profiles is important to advise local public health efforts regarding the appropriate treatment of SSTIs.

Triggerless data acquisition in asynchronous optical-sampling terahertz time-domain spectroscopy based on a dual-comb system.

By using two mutually phase-locked optical frequency combs with slightly different repetition rates, we demonstrate asynchronous optical-sampling terahertz time-domain spectroscopy (ASOPS THz-TDS) without using any trigger signals or optical delay lines. Due to a tight stabilization of the repetition frequencies, it was possible to accumulate the data over 48 minutes in a triggerless manner without signal degradation. The fractional frequency stability of the measured terahertz signal is evaluated to be ∼8.0 × 10-17 after 730 s. The frequency accuracy of the obtained terahertz spectrum is ensured by phase-locking the two frequency combs to a frequency standard. To clarify the performance of our system, we characterized the absorption line of water vapor around 0.557 THz. The good agreement of the measured center frequency and linewidth with the values predicted from the HITRAN database verifies the suitability of our ASOPS THz-TDS system for precise measurements.

Polarization-sensitive terahertz time-domain spectroscopy system without mechanical moving parts.

We report on the measurement of terahertz electric-field vector waveforms by using a system that contains no mechanical moving parts. It is known that two phase-locked femtosecond lasers with different repetition rates can be used to perform time-domain spectroscopy without using a mechanical delay stage. Furthermore, an electro-optic modulator can be used to perform polarization measurements without rotating any polarizers or waveplates. We experimentally demonstrate the combination of these two methods and explain the analysis of data obtained by such a system. Such a system provides a robust platform that can promote the usage of polarization-sensitive terahertz time-domain spectroscopy in basic science and practical applications. For the experimental demonstration, we alter the polarization of a terahertz wave with a polarizer.

Ultra-precise determination of thicknesses and refractive indices of optically thick dispersive materials by dual-comb spectroscopy.

Precise measurements of the geometrical thickness of a sample and its refractive index are important for materials science, engineering, and medical diagnosis. Among the possible non-contact evaluation methods, optical interferometric techniques possess the potential of providing superior resolution. However, in the optical frequency region, the ambiguity in the absolute phase-shift makes it difficult to measure these parameters of optically thick dispersive materials with sufficient resolution. Here, we demonstrate that dual frequency-comb spectroscopy can be used to precisely determine the absolute sample-induced phase-shift by analyzing the data smoothness. This method enables simultaneous determination of the geometrical thickness and the refractive index of a planar sample with a precision of five and a half digits. The thickness and the refractive index at 193.414 THz (λ = 1550 nm) of a silicon wafer determined by this method are 0.5204737(19) mm and 3.475625(58), respectively, without any prior knowledge of the refractive index.

Association between timing of speech and language therapy initiation and outcomes among post-extubation dysphagia patients: a multicenter retrospective cohort study.

BACKGROUND: Post-extubation dysphagia (PED) is recognized as a common complication in the intensive care unit (ICU). Speech and language therapy (SLT) can potentially help improve PED; however, the impact of the timing of SLT initiation on persistent PED has not been well investigated. This study aimed to examine the timing of SLT initiation and its effect on patient outcomes after extubation in the ICU. METHODS: We conducted this multicenter, retrospective, cohort study, collecting data from eight ICUs in Japan. Patients aged ≥ 20 years with orotracheal intubation and mechanical ventilation for longer than 48 h, and those who received SLT due to PED, defined as patients with modified water swallowing test scores of 3 or lower, were included. The primary outcome was dysphagia at hospital discharge, defined as functional oral intake scale score < 5 or death after extubation. Secondary outcomes included dysphagia or death at the seventh, 14th, or 28th day after extubation, aspiration pneumonia, and in-hospital mortality. Associations between the timing of SLT initiation and outcomes were determined using multivariable logistic regression. RESULTS: A total of 272 patients were included. Of them, 82 (30.1%) patients exhibited dysphagia or death at hospital discharge, and their time spans from extubation to SLT initiation were 1.0 days. The primary outcome revealed that every day of delay in SLT initiation post-extubation was associated with dysphagia or death at hospital discharge (adjusted odds ratio (AOR), 1.09; 95% CI, 1.02-1.18). Similarly, secondary outcomes showed associations between this per day delay in SLT initiation and dysphagia or death at the seventh day (AOR, 1.28; 95% CI, 1.05-1.55), 14th day (AOR, 1.34; 95% CI, 1.13-1.58), or 28th day (AOR, 1.21; 95% CI, 1.07-1.36) after extubation and occurrence of aspiration pneumonia (AOR, 1.09; 95% CI, 1.02-1.17), while per day delay in post-extubation SLT initiation did not affect in-hospital mortality (AOR, 1.04; 95% CI, 0.97-1.12). CONCLUSIONS: Delayed initiation of SLT in PED patients was associated with persistent dysphagia or death. Early initiation of SLT may prevent this complication post-extubation. A randomized controlled study is needed to validate these results.

Pharmacy responses during the COVID-19 pandemic: a questionnaire survey.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has heavily affected the economy, industries, and medicine. Local governments and medical institutions have struggled to respond. The purpose of this questionnaire survey was to evaluate strategies for pharmacy services, availability of ethanol for disinfection, and measures adopted for in-house infection control aiming to enhance future infection control efforts. METHODS: Since pharmacies have been also affected by the COVID-19 pandemic, we surveyed COVID-19 measures taken at 174 pharmacies in Ehime prefecture, Japan. RESULTS: The survey showed that pharmacies made changes to facilities and equipment, such as installing partitions at dispensing counters, procuring personal protective equipment for employees, and using ethanol for disinfection, even when these items were in short supply. Pharmacies also adopted new strategies, such as holding meetings with suppliers and internal staff via online platforms. Many pharmacies also undertook COVID-19 preventive measures, such as preparing documentation of infection control measures and disinfectants. Moreover, they held lectures and workshops on disinfection and infection control measures. CONCLUSIONS: From public health perspectives, pharmacies should adopt measures to prevent infections spread and, if necessary, utilise online tools and other new strategies to achieve this goal. It is also essential to educate the public about infection control, stockpile supplies, and work with hospitals to prevent COVID-19 spreads.

Within- and between-laboratory reproducibility and predictive capacity of amino acid derivative reactivity assay (ADRA) using a 0.5 mg/mL test chemical solution: Results of the study for reproducibility confirmation implemented in five participating laboratories.

The amino acid derivative reactivity assay (ADRA) is an in chemico alternative assay for skin sensitization listed in OECD test guideline 442C. ADRA evaluates the reactivity of sensitizers to proteins, which is key event 1 in the skin sensitization adverse outcome pathway. Although the current key event 1 evaluation method is a simple assay that evaluates nucleophile and test chemical reactivity, mixtures of unknown molecular weights cannot be evaluated because a constant molar ratio between the nucleophile and test chemical is necessary. In addition, because the nucleophile is quantified by HPLC, the frequency of co-eluting the test chemical and nucleophile increases when measuring multi-component mixtures. To solve these issues, test conditions have been developed using a 0.5 mg/mL test chemical solution and fluorescence-based detection. Since the practicality of these methods has not been substantiated, a validation test to confirm reproducibility was conducted in this study. The 10 proficiency substances listed in the ADRA guidelines were tested three times at five different laboratories. The results of both within- and between-laboratory reproducibility were 100%, and the results of ultraviolet- and fluorescence-based measurements were also consistent. In addition to the proficiency substances, a new positive control, squaric acid diethyl ester, was tested three times at the five laboratories. The results showed high reproducibility with N-(2-(1-naphthyl)acetyl)-l-cysteine depletion of 37%-52% and α-N-(2-(1-naphthyl)acetyl)-l-lysine depletion of 99%-100%. Thus, high reproducibility was confirmed in both evaluations of the 0.5 mg/mL test chemical and the fluorescence-based measurements, validating the practicability of these methods.

The within- and between-laboratories reproducibility and predictive capacity of Amino acid Derivative Reactivity Assay using 4 mM test chemical solution: Results of ring study implemented at five participating laboratories.

Amino acid derivative reactivity assay (ADRA) for skin sensitization was adopted as an alternative method in the 2019 OECD Guideline for the Testing of Chemicals (OECD TG 442C). The molar ratio of the nucleophilic reagent to the test chemicals in the reaction solution was set to 1:50. Imamura et al. reported that changing this molar ratio from 1:50 to 1:200 reduced in false negatives and improved prediction accuracy. Hence, a ring study using ADRA with 4 mM of a test chemical solution (ADRA, 4 mM) was conducted at five different laboratories to verify within- and between-laboratory reproducibilities (WLR and BLR, respectively). In this study, we investigated the WLR and BLR using 14 test chemicals grouped into three classes: (1) eight proficiency substances, (2) four test chemicals that showed false negatives in the ADRA with 1 mM test chemical solution (ADRA, 1 mM), but correctly positive in ADRA (4 mM), and (3) current positive control (phenylacetaldehyde) and a new additional positive control (squaric acid diethyl ester). The results showed 100% reproducibility and 100% accuracy for skin sensitization. Hence, it is clear that the ADRA (4 mM) is an excellent test method in contrast to the currently used ADRA (1 mM). We plan to resubmit the ADRA (4 mM) test method to the OECD Test Guideline Group in the near future so that OECD TG 442C could be revised for the convenience and benefit of many ADRA users.

Interferogram-based determination of the absolute mode numbers of optical frequency combs in dual-comb spectroscopy.

Dual-comb spectroscopy (DCS), which uses two optical frequency combs (OFCs), requires an accurate knowledge of the mode number of each comb line to determine spectral features. We demonstrate a fast evaluation method of the absolute mode numbers of both OFCs used in DCS system. By measuring the interval between the peaks in the time-domain interferogram, it is possible to accurately determine the ratio of one OFC repetition frequency (frep) to the difference between the frep values of the two OFCs (Δfrep). The absolute mode numbers can then be straightforwardly calculated using this ratio. This method is applicable to a broad range of Δfrep values down to several Hz without any additional instruments. For instance, the minimum required measurement time is estimated to be about 1 s for Δfrep ≈ 5.6 Hz and frep ≈ 60 MHz. The optical frequencies of the absorption lines of acetylene gas obtained by DCS with our method of mode number determination shows good agreement with the data from the HITRAN database.

Impact of urinary albumin excretion on the onset of adverse reactions to vancomycin hydrochloride.

OBJECTIVE: Vancomycin dose needs to be reduced for decreased kidney function; however, impact of urinary albumin excretion (UAE) on serum vancomycin level is unknown. In this study, we examined the factors associated with the onset of renal impairment induced by vancomycin by focusing on UAE. MATERIALS AND METHODS: The study included 52 patients who received vancomycin for methicillin-resistant Staphylococcus aureus at Ehime University Hospital between April 2010 and March 2015. To determine the presence of renal impairment, patients whose common terminology criteria for adverse-events (CTCAE) grade worsened by 1 or more comprised the renal impairment group, and multivariate logistic regression analysis was performed. RESULTS: 13 patients (25%) had renal impairment as indicated by a CTCAE grade change by 1 or more. The results of multivariate logistic regression analysis only of UAE (OR = 18.03; 95% CI = 1.97 - 164.89) was identified as a significant factor. CONCLUSION: We investigated the factors associated with the onset of renal impairment induced by vancomycin and identified UAE as a potential risk factor.

Successful blastocyst production by intracytoplasmic injection of sperm after in vitro maturation of follicular oocytes obtained from immature female squirrel monkeys (Saimiri boliviensis).

Advanced reproductive technologies are being applied for the propagation of squirrel monkeys, to ensure their preservation as a genetic resource and the effective use of their gametes in the future. In the present study, oocytes and spermatozoa were collected from live squirrel monkeys, following which piezo intracytoplasmic sperm injection (ICSI) was performed using these gametes. Follicular development was induced by administering equine chorionic gonadotropin (eCG) containing inhibin antiserum to an immature squirrel monkey female. The unilateral ovary was excised after the administration of human chorionic gonadotropin (hCG), to induce ovulation, following which the larger developed follicular oocytes were collected. Follicular oocytes were prepared for ICSI using sperm from the epididymal tail of a unilateral testis extracted from a mature male. The embryos were continuously incubated in CMRL 1066 medium supplemented with 10% (v/v) fetal bovine serum. Embryo culture was performed with cumulus cells. Two experiments of ICSI carried out with three females resulted in 14 mature oocytes from the 49 cumulus-oocyte complexes collected and five embryos, three of which developed into blastocysts. These blastocysts were vitrified, thawed, and transferred to recipient monkeys, but no pregnancies resulted. In conclusion, the present study is the first to successfully produce ICSI-derived blastocysts from MII oocytes obtained by means of hormone administration (a combination of eCG+inhibin antiserum and hCG) and in vitro maturation in immature squirrel monkeys.

Amino acid derivative reactivity assay-organic solvent reaction system: A novel alternative test for skin sensitization capable of assessing highly hydrophobic substances.

The amino acid derivative reactivity assay (ADRA) is an in chemico alternative to animal testing that focuses on protein binding. The ADRA is a skin sensitization test that solves problems associated with the direct peptide reactivity assay. However, when utilizing the ADRA to evaluate highly hydrophobic substances with octanol/water partition coefficients (logKow) of >6, the test substances may not dissolve in the reaction solution, which can prevent the accurate assessment of skin sensitization. Therefore, we developed the ADRA-organic solvent (ADRA-OS) reaction system, which is a novel skin sensitization test that enables the assessment of highly hydrophobic substances with a logKow of >6. We discovered that the organic solvent ratio, the triethylamine concentration, and the ethylenediaminetetraacetic acid disodium salt dihydrate concentration participate in reactions with the nucleophile N-(2-(1-naphthyl)acetyl)-l-cysteine (NAC) and sensitizers that are used in ADRA and in stabilizing NAC. Thus, we determined the optimal reaction composition of the ADRA-OS according to L9 (33 ) orthogonal array experiments. Using this test, we assessed 14 types of highly hydrophobic substances. When we compared the results with ADRA, we found that ADRA-OS reaction system has high solubility for highly hydrophobic substances and that it has a high predictive capacity (sensitivity: 63%, specificity: 100%, accuracy: 79%). The implication of the results is that the novel ADRA-OS reaction system should provide a useful method for assessing the skin sensitization of highly hydrophobic substances with a logKow of >6.

Application of Quantitative NMR Spectroscopy to the Quality Evaluation of Diclofenac Gargles as Hospital Preparations.

Hospital preparations are frequently prepared in Japanese hospitals when ready-made formulations to meet patients' needs are unavailable. Although the quality of hospital preparations have to be ensured for efficacy and safety, such quality evaluation tends to be insufficient mainly due to lack of manpower and experimental environments in hospitals. In this paper, we investigated the applicability of quantitative (q)NMR spectroscopy to the quality control of diclofenac gargles as examples of hospital preparations, as it has various merits for the quantitative analysis of mixtures in solutions. Diclofenac gargles are composed of diclofenac, tranexamic acid, and lidocaine, and are used for the pain relief of stomatitis induced by cancer chemotherapy. Aliquots of the gargles, which were prepared five times, were mixed with dimethylsulfone as an internal standard, followed by qNMR measurements. Water signal suppression was achieved using a pulse program, water suppression enhanced through T1 effects, because the pulse program was superior to other ones such as presaturation and one-dimensional nuclear Overhauser effect spectroscopy in terms of quantitativeness. Concentrations of the three medicinal ingredients were simultaneously determined based on the signals selected by considering the spectral separation and the quantitativeness. Consequently, the gargles were found to be prepared with constant quality, and were stable at room temperature for at least four weeks. qNMR is considered to be potentially useful for the quality control of various hospital preparations because of minimal sample pretreatments, lack of need of calibration curves, and its comprehensive detection abilities.

Early rehabilitation in older patients hospitalized with acute decompensated heart failure: A retrospective cohort study.

Although hospitalized patients with acute decompensated heart failure (ADHF) have severe physical dysfunction, little data are available on the comparative effectiveness of early versus late rehabilitation. This study examined the relationship between early compared to late rehabilitation and physical function among older patients hospitalized for ADHF. METHODS: In a retrospective cohort study, independent patients aged ≥65 years at baseline who were hospitalized for ADHF from 2012 to 2014 and underwent inpatient rehabilitation were identified using Emergency Department visit data and electronic medical records at two hospitals. Patients were classified into those who underwent early rehabilitation (initiated within 72 hours of admission) and late rehabilitation (after 72 hours). Primary outcome was length of time from admission until the patient was able to walk independently. Multivariable competing-risk regression with death as the competing event was used to adjust for potential confounding factors, and multiple imputation (MI) analysis was performed. RESULTS: Of 259 individuals, 30 (11.6%) commenced rehabilitation within 72 hours after admission while 229 (88.4%) did so 72 hours after admission. Patients who received early rehabilitation had a higher rate of unassisted walking for at least 40 m by 30 days after admission (hazard ratio: 8.03; 95% confidence interval: 2.15 to 29.98; P = .002 in the multivariable adjusted model) than those who received late rehabilitation. Similar findings were observed on MI analysis. CONCLUSION: Early rehabilitation therapy commenced within 72 hours of admission was associated with a higher rate of recovery of an activity of daily living (independent walking on a level surface).