Characterization of Bisphosphonate Hydrate Crystals by Phosphorus K-Edge X-Ray Absorption Near-Edge Structure Spectroscopy.

X-ray absorption near-edge structure (XANES) spectroscopy is a new method for the characterization of active pharmaceutical ingredients. XANES spectra show unique features depending on the electronic states of the X-ray absorbing elements and provide information about the chemical environment that affects the electronic states. In this study, six bisphosphonate hydrate crystals were used to investigate, for the first time, how the phosphorus K-edge XANES spectra are affected by the interatomic interactions and charged states of phosphonate moieties. Phosphorus K-edge XANES spectra showed several differences among the bisphosphonates. In particular, the chlorine atoms covalently bonded near the phosphonate and the number of electric charges of the phosphonate moieties seemed to have large effects on peak shape in XANES spectra. Unique shapes of the XANES spectra demonstrated that differences in interactions at the oxygen atoms of the phosphonate moieties could change the shapes of the XANES spectrum peaks to the extent that each material was distinguished based on the spectra. Since slight differences in interatomic interactions and charged states lead to variations in the spectra, XANES spectroscopy could be widely applied as the fingerprint method to evaluate active pharmaceutical ingredients.

Screen-printed wearable skin surface pH sensor for real-time monitoring of the buffering capacity of human skin.

This study demonstrated for the first time that skin surface pH can be monitored in real-time, using a screen-printed wearable pH sensor, to evaluate the buffering capacity of the human skin. The screen-printed pH sensor was composed of a polyaniline-based pH-sensitive electrode and a nitrocellulose membrane-based liquid junction type of Ag/AgCl reference electrode. This sensor showed a reliable and reversible potentiometric response to pH with long-term potential stability. Intermittent monitoring of the buffering capacity of skin surface pH demonstrated the reliability of the proposed wearable pH sensor, which was comparable to that of a commercially available flat-tip pH sensor. We found that contact of the wearable pH sensor with the subject's skin via aqueous electrolyte solutions was necessary for the sensor to continuously monitor the skin surface pH while sustaining the natural buffer capacity of the human skin surface.

Crystallization of Amorphous Nifedipine Under Isothermal Conditions: Inter-laboratory Reproducibility and Investigation of the Factors Affecting Reproducibility.

High inter-laboratory reproducibility is required for conducting collaborative experiments among several laboratories. The primary aim of our evaluation of the physical stability of amorphous drugs, conducted in co-operation with eight laboratories, was to establish a protocol for isothermal storage tests to obtain data of the same quality from all the participating laboratories. Sharing a protocol that contained the same level of detail as the experimental section of general papers was insufficient for high inter-laboratory reproducibility. We investigated the causes of variations in the data from the various laboratories and restricted the protocol step-by-step to achieve high inter-laboratory reproducibility. The various experimentalists had very different levels of awareness regarding how to control the temperature of a sample as the samples were transferred into and out of thermostatic chambers. Specific instructions on how to conduct this operation, such as regarding the time required for the transfer and thermal protection of the container during the transfer, helped to reduce variation. Improved inter-laboratory reproducibility revealed that the physical stabilities of amorphous drugs differed when samples were prepared in differently shaped aluminum pans designed for various differential scanning calorimeters.

Comparison of the physical properties of disodium etidronate amorphous forms prepared by different manufacturing methods.

Amorphous forms of disodium etidronate were prepared by three manufacturing methods, heat drying, freeze drying, and anti-solvent precipitation, and the effects of these methods on the physical properties of disodium etidronate amorphous forms were evaluated for the first time. Variable temperature X-ray powder diffraction and thermal analyses revealed that these amorphous forms had different physical properties such as glass transition point, water desorption, and crystallization temperatures. These differences can be explained by the molecular mobility and water content in amorphous forms. The differences in the structural characteristics related to the differences in these physical properties could not be detected clearly by the spectroscopic methods like Raman spectroscopy and X-ray absorption near-edge spectroscopy. Dynamic vapor sorption analyses demonstrated that all amorphous forms were hydrated to form I, a tetrahydrated form, at above 50% relative humidity, and the transition to form I was irreversible. These amorphous forms require strict humidity control to avoid crystallization. Among the three amorphous forms of disodium etidronate, the amorphous form prepared by heat drying was the most suitable for manufacturing the solid formulation, considering the low water content and low molecular mobility.

Prevalence of radiographic hip dysplasia in Japanese population-based study.

OBJECTIVES: The purpose of this study was to measure the indices of radiographic developmental dysplasia of the hip (DDH) in a cross-sectional study of an elderly Japanese population. METHODS: Hip radiographs of 427 informed, voluntary Japanese community-dwelling individuals (279 female and 148 male) aged 50-96 years-old were obtained from Miyagawa village in Japan through a health screening. The hip radiographs were measured by a custom-written, semi-automated MATLAB program. The center edge (CE) angle, acetabular roof obliquity (ARO), acetabular head index (AHI), and minimum joint space width (mJSW) were measured. We examined the associations between gender, side-of-hip, and age group on radiographic DDH and hip osteoarthritis (OA). RESULTS: The mean CE angle was 31.0°. The mean ARO was 5.8°. The mean AHI was 88.2%. The mean mJSW was 4.0 mm. Of the total population, 29.9% had DDH and 4.0% had hip OA. Of those who had hip OA, 41.2% were secondary OA, and 58.8% were primary OA. The relationship between DDH and OA was not significant. CONCLUSION: DDH is unlikely to be an important cause of hip OA in the present population-based study.

Highly Selective Hydrogenative Conversion of Nitriles into Tertiary, Secondary, and Primary Amines under Flow Reaction Conditions.

Flow reaction methods have been developed to selectively synthesize tertiary, secondary, and primary amines depending on heterogeneous platinum-group metal species under catalytic hydrogenation conditions using nitriles as starting materials. A 10 % Pd/C-packed catalyst cartridge affords symmetrically substituted tertiary amines in good to excellent yields. A 10 % Rh/C-packed catalyst cartridge enables the divergent synthesis of secondary and primary amines, with either cyclohexane or acetic acid as a solvent, respectively. Reaction parameters, such as the metal catalyst, solvent, and reaction temperature, and continuous-flow conditions, such as flow direction and second support of the catalyst in a catalyst cartridge, are quite important for controlling the reaction between the hydrogenation of nitriles and nucleophilic attack of in situ-generated amines to imine intermediates. A wide variety of aliphatic and aromatic nitriles could be highly selectively transformed into the corresponding tertiary, secondary, and primary amines by simply changing the metal species of the catalyst or flow parameters. Furthermore, the selective continuous-flow methodologies are applied over at least 72 h to afford three different types of amines in 80-99 % yield without decrease in catalytic activities.

Investigation of Physical Properties of Disodium Etidronate Tetrahydrate and Application of Phosphorus K-Edge X-Ray Absorption Near-Edge Structure Spectroscopy.

PURPOSE: Disodium etidronate is a bisphosphonate, compounds that are widely used in the treatment of bone disorders such as osteoporosis and Paget's disease. We investigated the physical properties of disodium etidronate tetrahydrate crystal, form I. METHODS: We used X-ray powder diffraction (XRPD), thermal analysis, dynamic vapor sorption (DVS), X-ray single crystal structure analysis, and phosphorus K-edge X-ray absorption near-edge structure (XANES) spectroscopy for the first time. RESULTS: XRPD and thermal analyses demonstrated that form I was dehydrated and transformed to an amorphous form, to a crystalline form II, and finally to a form III by heating. DVS measurements revealed that the amorphous form, form II, and form III were rehydrated to form I by humidification, and form I was stable even at 0% relative humidity. These results indicate that form I is the most stable solid-state under ambient conditions and is suitable as an API for manufacture in solid formulations. The phosphorus K-edge XANES spectra differed among form I, the amorphous form, and form II, which may be ascribed to the difference in the coordinate bond schemes between the phosphate moieties and sodium ions. The results demonstrated that the phosphorus K-edge XANES spectroscopy could be applied to the identification or the discrimination of crystal forms of the APIs containing phosphate moieties. CONCLUSIONS: Acquired information about physical properties are crucial for manufacturing of solid formulations of disodium etidronate. XANES spectroscopy is a promising alternative method for evaluating the solid-state forms of APIs.

Prevalence of and risk factors for hallux rigidus: a cross-sectional study in Japan.

BACKGROUND: Hallux rigidus (HR) is a common osteoarthritis of the first metatarsophalangeal joint. However, the epidemiology and risk factors of this pathology have yet to be clarified. METHODS: We have been conducting cohort studies among individuals over 50 years old every 2 years since 1997. This study analyzed data from the 7th to 10th checkups in 2009, 2011, 2013, and 2015. We investigated the prevalence of HR and its risk factors in a total of 604 individuals (mean age, 67.1 ± 6.4 years; 208 men, 396 women). Radiographic HR was defined as Hattrup and Johnson classification grade 1 or higher. Knee osteoarthritis (KOA) was scored according to the Kellgren-Lawrence grading system. Radiographic KOA was defined as grade 2 or higher. Cases with a hallux valgus (HV) angle of 20° or higher were defined as showing HV. Statistical analyses were performed using the Kruskal-Wallis test, Fisher's exact test, logistic regression modeling, and the Cochran-Armitage trend test. All p-values presented are two-sided and values of p < .05 were considered statistically significant. RESULTS: The prevalence of HR was 26.7% (161/604). Rates of grade 0, 1, 2, and 3 HR according to the Hattrup and Johnson classification were 73.3% (443/604), 16.4% (99/604), 8.0% (48/604), and 2.3% (14/604), respectively. Overall ratio of symptomatic HR was 8.1%. Univariate analysis revealed KOA, gout attack (GA), and HV as significantly associated with HR. The same factors were confirmed as independent risk factors for HR in multivariate analysis. All parameters were significantly associated with HR. Odds ratios of KOA, HV, and GA for HR were 1.73, 3.98, and 3.86, respectively. The presence or absence of KOA was significantly associated with severity of HR. CONCLUSIONS: This study revealed that the prevalence of HR in the elderly (≥50 years) was 26.7%. KOA, HV, and GA were independent risk factors for HR. KOA was associated with severity of HR.

Coronavirus Disease 2019 (COVID-19) Information for Cardiologists　- Systematic Literature Review and Additional Analysis.

BACKGROUND: Despite the rapidly increasing attention being given to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, more commonly known as coronavirus disease 2019 (COVID-19), the relationship between cardiovascular disease and COVID-19 has not been fully described.Methods and Results:A systematic review was undertaken to summarize the important aspects of COVID-19 for cardiologists. Protection both for patients and healthcare providers, indication for treatments, collaboration with other departments and hospitals, and regular update of information are essentials to front COVID-19 patients. CONCLUSIONS: Because the chief manifestations of COVID-19 infection are respiratory and acute respiratory distress syndrome, cardiologists do not see infected patients directly. Cardiologists need to be better prepared regarding standard disinfection procedures, and be aware of the indications for extracorporeal membrane oxygenation and its use in the critical care setting.

Locomotive syndrome testing in young and middle adulthood.

Background: Previous epidemiological studies on locomotive syndrome (LS) have been mainly conducted in retired elderly people. However, from the view point of its prevention, it is important to assess currently working younger people. The purpose of this study was to examine the status of the level of LS in young and middle-aged adult workers.Methods: This cross-sectional study was performed at four companies. We used the two-step test, stand-up test, and 25-question Geriatric Locomotive Function Scale (GLFS-25) as screening tools of LS. We also questioned the subjects for knee pain and low back pain.Results: A total of 715 workers participated in this study. The percentage of females with LS increased with age. However, the percentage of males with LS was approximately 20% in each age category. Two-step and stand-up test scores worsened in an age-dependent manner, although GLFS-25 scores varied independently of age. Knee pain, low back pain and physical activity were significantly related to LS-level.Conclusion: Our results suggest that there is some degree of LS even in young and middle-aged adults. Knee pain, low back pain and physical activity levels are key factors related to LS even in young and middle-aged adults.

Polyethyleneimine-Modified Polymer as an Efficient Palladium Scavenger and Effective Catalyst Support for a Functional Heterogeneous Palladium Catalyst.

The polyethyleneimine-modified polymers, polystyrene-divinylbenzene-based (TAs) and polymethacrylate-based polymers (TAm), were used as palladium scavengers to eliminate residual palladium species after palladium on carbon-catalyzed Sonogashira-type coupling reaction. Since both TAs and TAm indicated relatively favorable elimination abilities toward residual palladium species in the reaction mixture, the affinities of TAs and TAm for palladium species were used as supports for palladium catalysts. The TAm-supported palladium catalyst (Pd/TAm) indicated better catalyst properties for the chemoselective hydrogenation compared to those of the corresponding TAs-supported palladium catalyst (Pd/TAs). Aromatic benzyl ethers; aromatic and aliphatic N-Cbzs; and aromatic carbonyl groups were smoothly hydrogenated in the presence of 1-5 mol % of Pd/TAm in MeOH or 2-PrOH. In contrast, the hydrogenation of aromatic ketones was selectively suppressed in morpholine which act as appropriate catalyst poison and solvent. Furthermore, Pd/TAm-catalyzed chemoselective hydrogenation was applicable to continuous-flow reaction.

Does hallux valgus impair physical function?

BACKGROUND: The relationships between radiographic hallux valgus (HV) and various physical functions independent of knee osteoarthritis (KOA) were examined among residents of a mountain village in Japan. METHODS: Study participants were recruited from mountain village residents aged ≥50 years. Participants' height, weight, and body mass index (BMI) were measured, and baseline data, including age, sex, and foot pain, were obtained using interviews and questionnaires. Radiography of the feet and knees was performed to assess the presence of HV (HV angle ≥20°) and KOA (Kellgren-Lawrence grade ≥ II). Grip strength, 6-m walk at usual and maximum speeds, single-leg stance time, and stand up from a chair time were evaluated as physical function performance tests. Plantar pressure patterns were also examined. RESULTS: Moderate-severe HV (HV angle ≥30 degrees), impaired grip strength and maximum walking speed, and painful HV reduced usual and maximum walking speeds independent of KOA. Hallux plantar pressure decreased according to the HV angle. Hallux plantar pressure was significantly lower in painful HV than in the no HV feet or painless HV. CONCLUSIONS: Moderate-severe HV deformity and HV-related pain impaired physical function independent of KOA. By controlling the pain and severe deformity of HV by treatments such as surgery, the physical function of HV patients might be improved.

Development of a Tissue-Engineered Artificial Ligament: Reconstruction of Injured Rabbit Medial Collateral Ligament With Elastin-Collagen and Ligament Cell Composite Artificial Ligament.

Ligament reconstruction using a tissue-engineered artificial ligament (TEAL) requires regeneration of the ligament-bone junction such that fixation devices such as screws and end buttons do not have to be used. The objective of this study was to develop a TEAL consisting of elastin-coated polydioxanone (PDS) sutures covered with elastin and collagen fibers preseeded with ligament cells. In a pilot study, a ring-type PDS suture with a 2.5 mm (width) bone insertion was constructed with/without elastin coating (Ela-coat and Non-coat) and implanted into two bone tunnels, diameter 2.4 mm, in the rabbit tibia (6 cases each) to access the effect of elastin on the bond strength. PDS specimens taken together with the tibia at 6 weeks after implantation indicated growth of bone-like hard tissues around bone tunnels accompanied with narrowing of the tunnels in the Ela-coat group and not in the Non-coat group. The drawout load of the Ela-coat group was significantly higher (28.0 ± 15.1 N, n = 4) than that of the Non-coat group (7.6 ± 4.6 N, n = 5). These data can improve the mechanical bulk property of TEAL through extracellular matrix formation. To achieve this TEAL model, 4.5 × 106 ligament cells were seeded on elastin and collagen fibers (2.5 cm × 2.5 cm × 80 µm) prior to coil formation around the elastin-coated PDS core sutures having ball-shape ends with a diameter of 2.5 mm. Cell-seeded and cell-free TEALs were implanted across the femur and the tibia through bone tunnels with a diameter of 2.4 mm (6 cases each). There was no incidence of TEAL being pulled in 6 weeks. Regardless of the remarkable degradation of PDS observed in the cell-seeded group, both the elastic modulus and breaking load of the cell-seeded group (n = 3) were comparable to those of the sham-operation group (n = 8) (elastic modulus: 15.4 ± 1.3 MPa and 18.5 ± 5.7 MPa; breaking load: 73.0 ± 23.4 N and 104.8 ± 21.8 N, respectively) and higher than those of the cell-free group (n = 5) (elastic modulus: 5.7 ± 3.6 MPa; breaking load: 48.1 ± 11.3 N) accompanied with narrowed bone tunnels and cartilage matrix formation. These data suggest that elastin increased the bond strength of TEAL and bone. Furthermore, our newly developed TEAL from elastin, collagen, and ligament cells maintained the strength of the TEAL even if PDS was degraded.

Do exercise habits during middle age affect locomotive syndrome in old age?

OBJECTIVES: Locomotive syndrome (LS) encompasses conditions that may lead to the need for nursing services. We aimed to quantify the association between exercise habits during youth or the middle-age years and both physical function and the presence of LS in Japanese elderly people. METHODS: We examined 460 participants of the eighth, ninth, and tenth iterations of the Miyagawa study. Participants were divided into an LS group and a no-LS group according to their scores on the 25-question Geriatric Locomotive Function Scale. The following physical function tests were performed: grip strength, 6-m walk at normal and maximum speed, single-leg stance time with eyes open, and chair stand time. The frequency of past physical activity was determined by interview. RESULTS: Ninety-seven participants (21.1%) were classified as having LS. The LS group had worse physical function than the no-LS group. Exercise habits between the ages of 25 and 50 years were significantly related to later LS. CONCLUSIONS: Participants with LS were less likely to report a regular exercise habit between the ages of 25 and 50 years than participants without LS. Participants who reported regular exercise habits in middle age had better physical function during old age. Regular exercise habits in middle age appear to protect against LS during the older years.

Endoscopic All-inside Repair of the Flexor Hallucis Longus Tendon in Posterior Ankle Impingement Patients.

Longitudinal flexor hallucis longus (FHL) tendon tears are sometimes complicated by posterior ankle impingement syndrome (PAIS), especially in ballet dancers. In recent years, PAIS has been treated endoscopically, but it is difficult to suture FHL tendon tears endoscopically. In this report, we describe how to suture the FHL tendon endoscopically with the Meniscal Viper Repair system (Arthrex, Naples, FL). Without our endoscopic technique, when a patient is found to have a longitudinal tear of the FHL under endoscopy, we must choose to either neglect the tear or convert to an open repair. Open tendon suture techniques have reportedly had relatively good results but require a longer skin incision than endoscopic surgery for PAIS. Compared with the open repair, the advantages of our technique include earlier recovery, less pain, a lower rate of soft tissue complications, and improved healing through better preservation of the blood supply. This technique is an attractive and useful option because it is an easy and safe method for longitudinal FHL tendon tears.

Tendoscopic Double-Row Suture Bridge Peroneal Retinaculum Repair for Recurrent Dislocation of Peroneal Tendons in the Ankle.

Traumatic dislocation of peroneal tendons in the ankle is an uncommon lesion that mainly affects young adults. Unfortunately, most cases lead to recurrent dislocation of the peroneal tendons of the ankle (RPTD). Therefore, most cases need operative treatment. One of the most common operative procedures is superior peroneal retinaculum (SPR) repair. Recently, surgery for RPTD has been achieved with less invasive arthroscopic procedures. In this article, tendoscopic surgery for RPTD using a double-row suture bridge technique is introduced. This technique consists of debridement of the lateral aspect of the fibula under an intrasheath pseudo-cavity, suture anchor insertion into the fibular ridge, and reattachment of the SPR to the fibula using a knotless anchor screwed into the lateral aspect of the fibula. This technique mimics the double-row suture bridge technique for rotator cuff tear repair. The double-row suture bridge technique requires more surgical steps than the single-row technique, but it provides a wider bone-SPR contact surface and tighter fixation than the single-row technique. This procedure is an attractive option because it is less invasive and has achieved results similar to open procedures.

Exploring the predicted effect of social networking site use on perceived social capital and psychological well-being of Chinese international students in Japan.

This study investigated how social networking sites (SNSs) use by Chinese international students in Japan influenced their perceived social capital and psychological well-being. In addition, it examined how, as sojourners, Chinese international students' perceived acculturative stress varied. Data were collected from 142 Chinese international students. The results indicated that the intensity of SNS use was unable to predict individuals' perceived social capital and psychological well-being. The effect of SNS use varied according to the functions it serves. Specifically, SNS use for social and informational functions (SIF) increased individuals' levels of perceived bridging social capital and perceived life satisfaction, while SNS use for entertaining recreational functions (ERF) was unable to predict perceived social capital but increased individuals' levels of loneliness. It was also found that, in the intercultural environment, Chinese international students' levels of perceived acculturative stress were decreased by their perceived bonding social capital and increased by their perceived loneliness but had no relationship with their SNS use. Findings of the study suggest that individuals using SNSs to stay informed and connected will benefit with regard to their social network building and psychological well-being.

[Three advanced gastric cancer cases with liver metastases successfully treated by TS-1/CDDP combination therapy].

Three cases with unresectable advanced gastric cancer with liver metastases were successfully treated by the combination therapy of TS-1 and cisplatin( CDDP). TS-1 (1.25 m2>: 80 mg/day, 1.25 m2-1.50 m2: 100 mg/day, > or =1.50 m2: 120 mg/day) was administered orally for 14 consecutive days followed by 14 days rest,and a 24-h infusion of CDDP (70 mg/m2) was administered on day 8 of each course. Treatment was repeated every 4 weeks unless disease progression was observed. Partial response was obtained in all of the following three advanced gastric cancer cases with liver metastases. Case 1: 67-year-old male with Borrmann type I gastric cancer with multiple liver metastases. Case 2: 55-year-old female with multiple liver and lymph node metastases whose primary gastric lesion was surgically resected. Case 3: 53-year-old-male with Borrmann type III gastric cancer with liver and lymph node metastases. TS-1/CDDP therapy can be highly recommended for the treatment of advanced gastric cancer with liver metastases.