Effect of Centrality on Physical Activity in Late Childhood: A 1-Year Prospective Cohort Study.

BACKGROUND/OBJECTIVES: Engaging in physical activity (PA) is crucial for children's physical and mental health, with PA in childhood influencing lifelong activity levels. However, PA during childhood tends to decrease with age. Childhood friendship networks influence various health behaviors, including physical activity. Centralities are objective measures of an individual's position and role in friendship networks. The relationship between centrality and PA is inconsistent. This study aimed to determine how centrality affects changes in PA in late childhood longitudinally and to investigate the distribution of centrality in the network. METHODS: This prospective cohort study recruited fourth- and fifth-grade children (9-11 years old). A total of 143 children participated. We calculated three centralities-in-degree, closeness, and betweenness-based on social network analysis (SNA). PA was assessed using the physical activity questionnaire for older children (PAQ-C). To explore the relationship between centralities and the percentage change in PA, a multivariate logistic regression analysis was performed. RESULTS: Children with higher closeness had a significantly higher rate of decrease in PA after adjusting for confounding factors. There was no significant association between betweenness and percentage change in PA (p = 0.66) or in-degree and percentage change in PA (p = 0.21). CONCLUSIONS: This study highlights the importance of considering social network dynamics in PA interventions, particularly for children with high social closeness. Future research should incorporate objective PA measures and explore broader social networks to enhance intervention strategies, especially for Generation Z and Alpha, who experience unique opportunities and motivations for PA due to pervasive digital environments.

Life-Threatening Conditions and Preoperative Complications Associated with Cardiac Neoplasm Do Not Affect Surgical Outcomes or Mortality.

Background: Cardiac neoplasms may cause life-threatening symptoms associated with cerebral infarction, ventricular arrhythmias, and heart failure. Emergency surgery or preoperative treatment may be required for these patients. However, no study has reported the surgical outcomes in cases involving cardiac neoplasms with life-threatening complications. The current study investigated the mid- to long-term outcomes of surgery in patients with cardiac neoplasms in life-threatening conditions. Methods: This study retrospectively analyzed 36 consecutive patients who underwent resection for cardiac neoplasms with life-threatening cardiovascular, respiratory, and cerebral nervous system complications from January 2000 to December 2022. Their mean age at surgery was 54.9 years. In terms of fatal events, one patient who experienced a ventricular tachycardia storm caused by a left ventricular neoplasm was placed under deep sedation and managed with a ventilator preoperatively. Seven patients who presented with limb motor paralysis and visual defects had cerebral infarction. Two of the seven patients with cerebral infarction received cerebrovascular treatment before cardiac surgery. Results: During the follow-up period, cerebral- and cardiovascular-related deaths were not recorded. All postoperative cerebral and cardiovascular complications were new-onset cerebral infarction (n = 2) (with symptoms that improved during the long term). The mean follow-up period was 6.2 years. The 5- and 10-year survival rates of all patients were 89.8% and 78.7%, respectively. There were no significant differences in postoperative prognosis between patients with preoperative cerebral infarctions and those without. Conclusions: The long-term surgical outcome of patients with life-threatening symptomatic cardiac neoplasm was good. Thus, preoperative complications did not affect prognosis.

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.

Higher incidence of acute symptomatic seizures in probable antibody-negative pediatric autoimmune encephalitis than in major antibody-positive autoimmune encephalitis.

Purpose: To delineate the characteristics of probable antibody-negative pediatric autoimmune encephalitis (probable Ab-negative AE), we compared the clinical features of probable Ab-negative AE to those of major antibody-positive AE. Methods: We retrospectively reviewed the clinical features of 18 patients with probable Ab-negative AE, 13 with anti-N-methyl-D-aspartate receptor encephalitis (NMDARE), and 13 with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Clinical characteristics, neuroimaging findings, treatments, and outcomes were analyzed. Results: The age of onset and length of hospital stay were significantly higher in the NMDARE group than in the other groups (p = 0.02 and p < 0.01). Regarding initial neurological symptoms, acute symptomatic seizures in the probable Ab-negative AE group (67%) were significantly more frequent than in the NMDARE (15%) and MOGAD (23%) groups (p < 0.01). Paraclinical evidence of neuroinflammation within 1 month of disease onset revealed that single-photon emission computed tomography (SPECT) detected abnormal alterations in 14/14 (100%), cerebrospinal fluid (CSF) analysis in 15/18 (83%), and magnetic resonance imaging (MRI) in 11/18 (61%) in patients with probable Ab-negative AE. In the probable Ab-negative AE group, seven patients (39%) developed autoimmune-associated epilepsy, whereas one patient (8%) had both NMDARE and MOGAD (not statistically significant, p = 0.07). Conclusion: Patients with probable Ab-negative AE exhibited acute symptomatic seizures as initial neurological symptoms significantly more frequently. They developed autoimmune-associated epilepsy more frequently than those with NMDARE and MOGAD, which was not statistically significant. SPECT within 1 month of disease onset might be a valuable surrogate marker of ongoing neuroinflammation and neuronal dysfunction, even in patients with negative MRI findings.

Molecular Dynamics Simulation of Cumulative Microscopic Damage in a Thermosetting Polymer under Cyclic Loading.

To develop durable composite materials, it is crucial to elucidate the correlation between nanoscale damage in thermosetting resins and the degradation of their mechanical properties. This study aims to investigate this correlation by performing cyclic loading tests on the cross-linked structure of diglycidyl ether bisphenol A (DGEBA) and 4,4'-diaminodiphenyl sulfone (44-DDS) using all-atom molecular dynamics (MD) simulations. To accurately represent the nanoscale damage in MD simulations, a bond dissociation algorithm based on interatomic distance criteria is applied, and three characteristics are used to quantify the microscopic damage: stress-strain curves, entropy generation, and the formation of voids. As a result, the number of covalent bond dissociations increases with both the cyclic loading and its amplitude, resulting in higher entropy generation and void formation, causing the material to exhibit inelastic behavior. Furthermore, our findings indicate the occurrence of a microscopic degradation process in the cross-linked polymer: Initially, covalent bonds align with the direction of the applied load. Subsequently, tensioned covalent bonds sequentially break, resulting in significant void formation. Consequently, the stress-strain curves exhibit nonlinear and inelastic behavior. Although our MD simulations employ straightforward criteria for covalent bond dissociation, they unveil a distinct correlation between the number of bond dissociations and microscale damage. Enhancing the algorithm holds promise for yielding more precise predictions of material degradation processes.

Click3D: Click reaction across deep tissues for whole-organ 3D fluorescence imaging.

Click chemistry offers various applications through efficient bioorthogonal reactions. In bioimaging, pretargeting strategies have often been used, using click reactions between molecular probes with a click handle and reporter molecules that make them observable. Recent efforts have integrated tissue-clearing techniques with fluorescent labeling through click chemistry, allowing high-resolution three-dimensional fluorescence imaging. Nevertheless, these techniques have faced a challenge in limited staining depth, confining their use to imaging tissue sections or partial organs. In this study, we introduce Click3D, a method for thoroughly staining whole organs using click chemistry. We identified click reaction conditions that improve staining depth with our custom-developed assay. The Click3D protocol exhibits a greater staining depth compared to conventional methods. Using Click3D, we have successfully achieved whole-kidney imaging of nascent RNA and whole-tumor imaging of hypoxia. We have also accomplished whole-brain imaging of hypoxia by using the clickable hypoxia probe, which has a small size and, therefore, has high permeability to cross the blood-brain barrier.

Survey on diagnosis of post-brain injury "higher brain dysfunction" in patients with cognitive impairment. Family/caregiver response.

In Japan, the diagnostic criteria for the higher brain dysfunction (HBD) emerged in 2005 in response to social needs for support for the patients and their families. The issue of cognitive dysfunction after brain trauma is not unique to Japan. The purpose of this study was to reveal the current status of family members of HBD patients from their perspective, focusing on the changes before and after the establishment of diagnostic criteria in Japan. We conducted a questionnaire survey for family members supporting the HBD patients. The questionnaire included the causative condition, explanation on HBD by health professionals, and problems/difficulties they encountered. This research involved family members of 278 HBD cases (males = 211, age 49 years). The major underlying cause was head injury (n = 139). Compared to patients diagnosed pre-2005, a significantly larger proportion of family members after 2005 received information on the condition during the acute phase (within one month) (p < 0.001), including that from physicians (p < 0.001). Nearly half of the families cited a lack of awareness of HBD among the professionals as a problem. In Japan, awareness of HBD in the society is gradually increasing especially after the current diagnostic criteria were implemented, and there has been a steady increase over time in early diagnosis. Yet, there still remain those not appropriately diagnosed. To salvage those patients and the families left behind, we are suggesting several recommendations to further augment clinical practice and the healthcare systems in Japan.

Characteristics of malignant brain tumor-associated epileptic spasms.

Although epilepsy is the most common comorbidity of brain tumors, epileptic spasms rarely occur. Brain tumors associated with epileptic spasms are mostly low-grade gliomas. To date, few studies in the literature have reported on malignant (Grades 3-4) brain tumors associated with epileptic spasms. Thus, we aimed to investigate the characteristics of malignant brain tumor-associated epileptic spasms. We retrospectively reviewed patients with malignant brain tumors and epileptic spasms in our institution. Data on demographics, tumor histology, magnetic resonance imaging, epileptic spasm characteristics, electroencephalography, and treatment responsiveness were also collected. Six patients were included. In all cases, the brain tumors occurred in infancy in the supratentorial region and epileptic spasm onset occurred after the completion of brain tumor treatment. Anti-seizure medication did not control epileptic spasms; two patients were seizure-free after epileptic surgery. Although all patients had developmental delays caused by malignant brain tumors and their treatment, developmental regression proceeded after epileptic spasm onset. Two patients who achieved seizure-free status showed improved developmental outcomes after cessation of epileptic spasms. This is the first report of the characteristics of malignant brain tumor-associated epileptic spasms. Our report highlights a difficulties of seizure control and possibillity of efficacy of epileptic surgery in this condition. In malignant brain tumor-associated epileptic spasms, it is important to proceed with presurgical evaluation from an early stage, bearing in mind that epileptic spasms may become drug-resistant.

Successful Hemispherotomy in a Patient With 22q11.2 Deletion Syndrome Who Had Developmental and Epileptic Encephalopathy With Spike-and-Wave Activation During Sleep.

We report a case of developmental and epileptic encephalopathy with spike-and-wave activation during sleep with 22q11.2 deletion syndrome in a patient who had undergone hemispherotomy and achieved developmental improvement. A four-year-old male child with paralysis on the left side of his body since birth had a mild developmental delay. An MRI of the brain revealed polymicrogyria diffusely throughout the right hemisphere. He was diagnosed with the 22q11.2 deletion syndrome at one year of age. Focal impaired awareness seizure in the right hemisphere origin and focal to bilateral tonic-clonic seizure appeared by two years of age. At three years of age, myoclonic seizures occurred, which induced frequent falls. Simultaneously, developmental and epileptic encephalopathy with spike-and-wave activation during sleep were observed. At four years and seven months of age, the patient underwent a right hemispherotomy. Epileptic seizures and spike-and-wave activation during sleep disappeared, and cognitive improvement was observed one year after surgery. In spite of chromosomal abnormalities being present, drug-resistant epilepsy with localized regions on MRI should be evaluated to determine surgical options to improve cognitive function and development.

A 10-Year Study of the Trend of Accidental Falls in the Elderly in a Japanese Hospital.

Elderly people are prone to falls. We established the Falls Prevention Working Group (FPWG) at our hospital in 2015 to reduce the number of falls during hospitalization. This study compared the trend of in-hospital falls in the elderly in two time periods (2008/9 and 2018/9) and determined the effects of FPWG-implemented measures. Using medical records, we counted the monthly number of falls suffered by patients during hospitalization in April 2008-March 2009 and April 2018-March 2019. We also categorized the falls according to the severity of fall-related complications.A total of 3609 hospital falls were recorded during the 2008-2019 period (2008/9: n = 433, 2018/9: n = 324). Falls were more common in patients aged 70-79 in 2008/9 but were noted in those aged ≥ 80 in 2018/9. The mean number of falls/month (27.3 ± 6.4, range: 12-45) was stable throughout the year. The incidence of falls in 2018/9 (1.90/1000 per persons per day) was significantly lower than in 2008/9 (2.30/1000, p = 0.006). Level ≥ 3b accidents, reflecting serious accidents with complications, were encountered in 12 of 433 accidents in 2008/9 compared with significantly fewer accidents (2 of the same severity among 324 accidents) in 2018/9 (p = 0.030).Our results showed a decrease in in-hospital falls in 2018/9 and that the sufferers were older relative to 10 years earlier. A multidisciplinary team should recommend measures to prevent falls and an environment "resilient" to falls, and encourage patients to be aware of possible falls.

Pimonidazole-alkyne conjugate for sensitive detection of hypoxia by Cu-catalyzed click reaction.

Hypoxia is involved in various diseases, such as cancers. Pimonidazole has often been used as the gold-standard marker to visualize hypoxic regions. Pimonidazole labels hypoxic regions by forming a covalent bond with a neighboring protein under hypoxic conditions in the body, which is detected by immunohistochemistry performed on tissue sections. To date, some pimonidazole-fluorophore conjugates have been reported as fluorescent probes for hypoxia imaging that do not require immunostaining. They are superior to pimonidazole because immunostaining can produce high background signals. However, large fluorophores in the conjugates may alter the original biodistribution and reactivity. Here, we report a new hypoxia marker, Pimo-yne, as a pimonidazole-alkyne conjugate. Pimo-yne has a similar hypoxia detection capability as pimonidazole because the alkyne tag is small and can be detected by Cu-catalyzed click reaction with azide-tagged fluorescent dyes. We successfully visualized hypoxic regions in tumor tissue sections using Pimo-yne with reduced background signals. The detected regions overlapped well with those detected by pimonidazole immunohistochemistry. To further reduce the background, we employed a turn-on azide-tagged fluorescent dye.

Whole-Body and Whole-Organ 3D Imaging of Hypoxia Using an Activatable Covalent Fluorescent Probe Compatible with Tissue Clearing.

Elucidation of biological phenomena requires imaging of microenvironments in vivo. Although the seamless visualization of in vivo hypoxia from the level of whole-body to single-cell has great potential to discover unknown phenomena in biological and medical fields, no methodology for achieving it has been established thus far. Here, we report the whole-body and whole-organ imaging of hypoxia, an important microenvironment, at single-cell resolution using activatable covalent fluorescent probes compatible with tissue clearing. We initially focused on overcoming the incompatibility of fluorescent dyes and refractive index matching solutions (RIMSs), which has greatly hindered the development of fluorescent molecular probes in the field of tissue clearing. The fluorescent dyes compatible with RIMS were then incorporated into the development of activatable covalent fluorescent probes for hypoxia. We combined the probes with tissue clearing, achieving comprehensive single-cell-resolution imaging of hypoxia in a whole mouse body and whole organs.

Pneumococcal vaccination coverage and vaccination-related factors among older adults in Japan: LIFE Study.

PURPOSE: To investigate individual and environmental vaccination-related factors among the older adults in Japan, using administrative data. METHODS: We conducted a cohort study and included people who reached the relevant age (≥65 years) for routine pneumococcal vaccination of older adults between April 2015 and March 2020. Monthly data of residents in the two municipalities from April 2014 to March 2020 and vaccination records from April 2015 to March 2020 were used. We defined five cohorts according to the year in which routine vaccinations were available. Each cohort was followed for a total of two years, with the first year being the "baseline period" and second year being the "vaccine follow-up period." Pneumococcal vaccination data was extracted from vaccination records at "first dose." Age, sex, socioeconomic status, comorbidities, hospital visit history, hospitalization history, Specific Health Check-ups participation, and information on contracted hospitals for pneumococcal vaccination were used as covariates. A multivariate logistic regression model was used to investigate the relationship between pneumococcal vaccination and vaccination-related factors. Odds ratios (OR) and 95 % confidence intervals (95 % CI) were calculated. RESULTS: Analysis included 17,991 patients. Vaccination coverage was 33.6 % for all subjects. Multivariate analysis found the following as significant vaccination-related factors: female (OR: 1.18, 95 % CI: 1.11-1.26), not low income (1.76, 1.17-2.76), hospital visits: ≥once/month (1.27, 1.19-1.35), and Specific Health Check-ups participation (2.10, 1.95-2.27). No significant results were found for hospitals that contracted pneumococcal vaccination. CONCLUSIONS: Individual factors, such as sex and Specific Health Check-ups participation, were found to be important factors affecting pneumococcal vaccination among older adults in Japan. Environmental factors, such as the characteristics of residential areas, should be evaluated in further investigations.

Cilostazol treats transient heart failure caused by ATP1A3 variant-associated polymicrogyria.

BACKGROUND: Some patients with ATP1A3 variant-associated polymicrogyria have recurrent transient heart failure. However, effective treatment for the transient cardiac condition remains to be elucidated. CASE REPORT: The patient started experiencing focal motor onset seizures in 12 h after birth, revealing bilateral diffuse polymicrogyria. The patient also experienced transient bradycardia (sinus bradycardia) attacks from 15 days old. Echocardiography revealed a reduced ejection fraction; however, no obvious electrocorticogram or electroencephalogram abnormalities were observed during the attacks. Initially, the attacks occurred in clusters daily. They later decreased in frequency, occurring at monthly intervals. Repeated episodes of transient bradycardia attacks and polymicrogyria indicated possible ATP1A3 gene abnormality and genetic testing revealed a novel heterozygous ATP1A3 variant (NM_152296: exon22:c.2977_2982del:p.(Glu993_Ile994del)), which was not found in the patient's parents. Cilostazol was administered at 3 months old for recurrent transient bradycardia attacks. Cilostazol significantly shortened the duration of bradycardia episodes and prolonged the interval between attacks. Cilostazol also effectively treats transient symptomatic bradycardia. CONCLUSION: Cilostazol could be a treatment option for recurrent transient bradycardia attacks associated with ATP1A3 gene abnormalities and polymicrogyria.

Abnormal axonal development and severe epileptic phenotype in Dynamin-1 (DNM1) encephalopathy.

Dynamin-1 (DNM1) is involved in synaptic vesicle recycling, and DNM1 mutations can lead to developmental and epileptic encephalopathy. The neuroimaging of DNM1 encephalopathy has not been reported in detail. We describe a severe phenotype of DNM1 encephalopathy showing characteristic neuroradiological features. In addition, we reviewed previously reported cases who have DNM1 pathogenic variants with white matter abnormalities. Our case presented drug-resistant seizures from 1 month of age and epileptic spasms at 2 years of age. Brain MRI showed no progression of myelination, progression of diffuse cerebral atrophy, and a thin corpus callosum. Proton magnetic resonance spectroscopy showed a decreased N-acetylaspartate peak and diffusion tensor imaging presented with less pyramidal decussation. Whole-exome sequencing revealed a recurrent de novo heterozygous variant of DNM1. So far, more than 50 cases of DNM1 encephalopathy have been reported. Among these patients, delayed myelination occurred in two cases of GTPase-domain DNM1 encephalopathy and in six cases of middle-domain DNM1 encephalopathy. The neuroimaging findings in this case suggest inadequate axonal development. DNM1 is involved in the release of synaptic vesicles with the inhibitory transmitter GABA, suggesting that GABAergic neuron dysfunction is the mechanism of refractory epilepsy in DNM1 encephalopathy. GABA-mediated signaling mechanisms play important roles in axonal development and GABAergic neuron dysfunction may be cause of white matter abnormalities in DNM1 encephalopathy.

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.

Surveys of eleven species of wild and zoo birds and feeding experiments in white-tailed eagles reveal differences in the composition of the avian gut microbiome based on dietary habits between and within species.

The composition of the gut microbiome varies due to dietary habits. We investigated influences of diet on the composition of the gut microbiome using the feces of 11 avian species, which consumed grain-, fish- and meat-based diets. We analyzed gut microbiome diversity and composition by next-generation sequencing (NGS) of 16S ribosomal RNA. The grain-diet group had higher gut microbiome diversity than the meat- and fish-diet group. The ratio of Bacteroidetes and Firmicutes phyla was higher in the grain-diet group than in the meat- and fish-diet groups. The grain-diet group had a higher ratio of Veillonellaceae than the meat-diet group and a higher ratio of Eubacteriaceae than the fish-diet habit group. To clarify the influence of diet within the same species, white-tailed eagles (Haliaeetus albicilla, n=6) were divided into two groups, and given only deer meat or fish for approximately one month. The composition of the gut microbiome of individuals in both groups were analyzed by NGS. There were indications of fluctuation in the levels of some bacteria (Lactobacillus, Coriobacteriales, etc.) in each diet group. Moreover, one individual for each group which switched each diet in last week changed to each feature of composition of bacterial flora. The above results show that the composition of the gut microbiome differ depending on diet, even within the same species.

Multimodal treatment, including extracorporeal shock wave therapy, for refractory chronic tension-type headache: a case report.

BACKGROUND: Few reports have described multidisciplinary treatment, including extracorporeal shock wave therapy, for patients with refractory chronic tension-type headache. In this study, we conducted multidisciplinary treatment for a patient with chronic tension-type headache who suffered from chronic headache refractory to treatment. CASE PRESENTATION: The patient was a 45-year-old Japanese male suffering from 20 years of headache. As his headache had worsened recently, he visited a local clinic. With the diagnosis of suspected tension-type headache, its treatment was unsuccessful and he was referred to our hospital. The neurology department confirmed the tension-type headache and prescribed another medication, but he showed no improvement. Then, the patient was referred to the rehabilitation medicine department for consultation. At the initial visit, we identified multiple myofascial trigger points in his bilateral posterior neck and upper back regions. At the initial visit, he was prescribed 10 mL of 1% lidocaine injected into the muscles in these areas. In addition, he received 2000 extracorporeal shock wave therapy into bilateral trapezius muscles, and was instructed to take oral Kakkonto extract granules, benfotiamine, pyridoxine hydrochloride, and cyanocobalamin. Cervical muscle and shoulder girdle stretches and exercises were also recommended. At follow-up treatment visits, we used extracorporeal shock wave therapy to bilateral trapezius muscles, which led to immediate pain relief. After 11 weeks, he was not taking any medication and his headache was subjectively improved and his medical treatment ended. CONCLUSION: A patient with chronic tension-type headache refractory to regular treatment was successfully treated with a multimodal approach including extracorporeal shock wave therapy in addition to standard treatment. For patients with tension-type headache accompanied by myofascial trigger points, it may be recommended to promptly consider aggressive multimodal treatment that includes extracorporeal shock wave therapy.

Transvascular delivery of talaporfin sodium to subcutaneous tumors in mice by nanosecond pulsed laser-induced photomechanical waves.

BACKGROUND: We previously developed a site-specific transvascular drug delivery system (DDS) based on photomechanical waves (PMWs) or laser-induced stress/shock waves (LISWs). In this study, we investigated the validity of this method to deliver a clinical photosensitizer, talaporfin sodium (TS), to subcutaneous tumors in mice and to enhance the efficacy of photodynamic therapy (PDT). METHODS: TS solution (2.5 mg/kg) was intravenously injected into mice. Immediately thereafter, PMWs were applied to the tumor by irradiating a laser target with a Q-switched ruby laser pulse (0.8 J/cm2). Five hours after TS administration, some tumors were excised to evaluate the depth distribution of the delivered TS under a fluorescence microscope. Other tumors were subjected to PDT by irradiating the tissues with a 665 nm continuous-wave laser diode (75 mW/cm2, 667 s) at this timepoint. The effects of PDT were evaluated on the basis of the two primary therapeutic mechanisms of TS-mediated PDT: i) damage to tumor cells and ii) damage to endothelial cells of tumor vessels, i.e., the vascular shutdown effect on tumors. RESULTS: PMW application significantly increased the accumulation of TS in the tumor parenchyma but not in the tumor vessel walls; the endothelial cell junctions of tumor vessels should be the route of TS delivery enhanced by PMWs. Thus, as a result of PMW application followed by PDT, while the vascular shutdown effect on the tumors was not enhanced, direct damage to the tumor cells was increased, resulting in significant tumor growth retardation without body weight loss for 7 days after treatment.