Cerebral blood flow abnormalities with central sparing on arterial spin labeling in mild encephalopathy associated with excitotoxicity: a case report.

BACKGROUND: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) and mild encephalopathy associated with excitotoxicity (MEEX) are the most frequent acute encephalopathies in pediatric patients in Japan. AESD typically presents with biphasic seizures and delayed reduced diffusion in the subcortical area, called bright tree appearance (BTA), on radiological examination. In patients with AESD, arterial spin labeling (ASL) shows decreased cerebral blood flow (CBF) in the hyperacute stage and increased CBF in the acute stage, suggesting the usefulness of ASL for the early diagnosis of AESD. Additionally, proton magnetic resonance spectroscopy (MRS) shows elevated glutamate (Glu) and glutamine (Gln) in AESD. MEEX is a group of mild encephalopathies with transient elevation of Gln on MRS similar to that in AESD; however, MEEX does not include any clinical biphasic course or abnormalities, including BTA on diffusion-weighted imaging. Although the usefulness of ASL for AESD has been reported, there are no reports for patients with MEEX. In this study, we report our experience with a 4-year-old girl diagnosed with MEEX who showed unique findings on ASL. CASE PRESENTATION: The patient was a 4-year-old girl admitted to the emergency room with febrile status epilepticus. Considering the possibility of AESD, vitamin therapy was initiated. ASL-MR imaging (MRI) of the brain performed on the second day showed increased blood flow in the frontal, temporal, and occipital regions with spared central sulcus, which indicated AESD with central sparing. The patient was diagnosed with AESD, and the treatment included pulse steroid therapy and immunoglobulin therapy from day 3. The patient remained mildly unconscious but gradually became conscious by day 7 with no seizures. Brain MRI performed on day 8 did not show any characteristic AESD findings, such as BTA. Furthermore, MRS showed elevated Gln, which, along with the clinical course, led to the diagnosis of MEEX. The patient was discharged on day 16 without obvious sequelae. CONCLUSIONS: ASL may be useful in the early diagnosis of MEEX as well as AESD, facilitating early intervention.

Chronic active EBV infection in refractory enteritis with longitudinal ulcers with a cobblestone appearance: an autopsied case report.

BACKGROUND: Chronic active Epstein-Barr virus infection (CAEBV) is defined as Epstein-Barr virus (EBV)-positive T/NK cell-related neoplasia, and its major clinical symptom is systemic inflammation presenting as infectious mononucleocytosis, whereas enteritis and diarrhea are minor clinical symptoms. The complex mixture of tumorigenic processes of EBV-positive cells and physical symptoms of systemic inflammatory disease constitutes the varied phenotypes of CAEBV. Herein, we describe a case of CAEBV that was initially diagnosed as Crohn's disease (CD) based on ileal ulcers and clinical symptoms of enteritis. CASE PRESENTATION: A 19-year-old woman complained of abdominal pain and fever. Blood examination showed normal blood cell counts without atypical lymphocyte but detected modest inflammation, hypoalbuminemia, slight liver dysfunction, and evidence of past EBV infection. The esophagogastroduodenoscopic findings were normal. However, colonoscopy revealed a few small ulcers in the terminal ileum. The jejunum and ileum also exhibited various forms of ulcers, exhibiting a cobblestone appearance, on capsule endoscopy. Based on these clinical findings, she was strongly suspected with CD. In the course of treatment by steroid and biologics for refractory enteritis, skin ulcers appeared about 50 months after her initial hospital visit. Immunohistology of her skin biopsy revealed proliferation of EBV-encoded small RNA (EBER)-positive atypical lymphocytes. We retrospectively assessed her previous ileal ulcer biopsy before treatment and found many EBER-positive lymphocytes. Blood EBV DNA was also positive. Therefore, she was diagnosed with extranodal NK/T-cell lymphoma with CAEBV-related enteritis rather than CD. She was treated with cyclosporine and prednisolone combination therapy for CAEBV-related systemic inflammation and chemotherapy for malignant lymphoma. Unfortunately, her disease continued to progress, leading to multiple organ failure and death at the age of 23 years. CONCLUSION: Clinicians need to remember the possibility of CAEBV as a differential diagnosis of refractory enteritis. Enteritis with intestinal ulcer is a rare symptom of CAEBV, and it is impossible to acquire a definitive diagnosis by ulcer morphology only. In cases where the possibility of CAEBV remains, tissue EBVR expression should be checked by in situ hybridization and blood EBV DNA.

Efficacy and safety of intravesical instillation of KRP-116D (50% dimethyl sulfoxide solution) for interstitial cystitis/bladder pain syndrome in Japanese patients: A multicenter, randomized, double-blind, placebo-controlled, clinical study.

OBJECTIVE: To evaluate the efficacy and safety of intravesical KRP-116D, 50% dimethyl sulfoxide solution compared with placebo, in interstitial cystitis/bladder pain syndrome patients. METHODS: Japanese interstitial cystitis/bladder pain syndrome patients with an O'Leary-Sant Interstitial Cystitis Symptom Index score of ≥9, who exhibited the bladder-centric phenotype of interstitial cystitis/bladder pain syndrome diagnosed by cystoscopy and bladder-derived pain, were enrolled. Patients were allocated to receive either KRP-116D (n = 49) or placebo (n = 47). The study drug was intravesically administered every 2 weeks for 12 weeks. RESULTS: For the primary endpoint, the change in the mean O'Leary-Sant Interstitial Cystitis Symptom Index score from baseline to week 12 was -5.2 in the KRP-116D group and -3.4 in the placebo group. The estimated difference between the KRP-116D and placebo groups was -1.8 (95% confidence interval -3.3, -0.3; P = 0.0188). Statistically significant improvements for KRP-116D were also observed in the secondary endpoints including O'Leary-Sant Interstitial Cystitis Problem Index score, micturition episodes/24 h, voided volume/micturition, maximum voided volume/micturition, numerical rating scale score for bladder pain, and global response assessment score. The adverse drug reactions were mild to moderate, and manageable. CONCLUSIONS: This first randomized, double-blind, placebo-controlled trial shows that KRP-116D improves symptoms, voiding parameters, and global response assessment, compared with placebo, and has a well-tolerated safety profile in interstitial cystitis/bladder pain syndrome patients with the bladder-centric phenotype.

Contribution of anti-inflammatory and anti-virulence effects of azithromycin in the treatment of experimental Staphylococcus aureus keratitis.

BACKGROUND: We aimed to demonstrate the contribution of anti-inflammatory and anti-virulence effects of azithromycin (AZM) in ocular surface infection treatment. METHODS: Staphylococcus aureus was injected into the corneal stroma of rabbits to induce keratitis. AZM at concentrations of 0.01, 0.1, and 1% was instilled into the eye twice daily. The eyes were examined using a slit lamp and scored. The viable bacteria in the cornea were counted at 48 h post infection. To evaluate the anti-inflammatory efficacy of AZM, S. aureus culture supernatant-induced anterior ocular inflammation in rabbit was examined using a slit lamp and scored. To evaluate the inhibitory effect of AZM on bacterial toxin production, S. aureus was cultured with AZM and hemolytic reaction in the culture supernatant was determined. RESULTS: In the bacterial keratitis model, AZM dose-dependently inhibited the increase in the clinical score. The viable bacterial count in the cornea treated with 1% AZM significantly decreased compared with that of the vehicle, whereas bacterial count in 0.01 and 0.1% AZM-treated corneas was similar to that of the vehicle. In the anterior ocular inflammation model, 0.1 and 1% AZM inhibited the increase in the clinical score. AZM inhibited hemolytic reaction at concentrations that did not inhibit bacterial growth. CONCLUSIONS: The results demonstrated that AZM has not only anti-bacterial, but also anti-inflammatory effects, and inhibits bacterial toxin production leading to ocular surface damage in bacterial infection. Thus, the therapeutic effect of AZM against ocular infections is expected to be higher than that which could be assumed if it only had anti-bacterial activity.

Doxorubicin Expands in Vivo Secretion of Circulating Exosome in Mice.

Modulation of tumor immunity is a known factor in the antitumor activity of many chemotherapeutic agents. Exosomes are extracellular nanometric vesicles that are released by almost all types of cells, which includes cancer cells. These vesicles play a crucial role in tumor immunity. Many in vitro studies have reproduced the aggressive secretion of exosomes following treatment with conventional anticancer drugs. Nevertheless, how chemotherapeutic agents including nanomedicines such as Doxil® affect the in vivo secretion of exosomes is yet to be elucidated. In this study, the effect of intravenous injection of either free doxorubicin (DXR) or liposomal DXR formulation (Doxil®) on exosome secretion was evaluated in BALB/c mice. Exosomes were isolated from serum by using an ExoQuick™ kit. Free DXR treatment markedly increased serum exosome levels in a post-injection time-dependent manner, while Doxil® treatment did not. Exosomal size distribution and marker protein expressions (CD9, CD63, and TSG101) were studied. The physical/biological characteristics of treatment-induced exosomes were comparable to those of control mice. Interestingly, splenectomy significantly suppressed the copious exosomal secretions induced by free DXR. Collectively, our results indicate that conventional anticancer agents induce the secretion of circulating exosomes, presumably via stimulating immune cells of the spleen. As far as we know, this study represents the first report indicating that conventional chemotherapeutics may induce exosome secretion which might, in turn, contribute partly to the antitumor effect of chemotherapeutic agents.

Commonly stabilized cytochromes c from deep-sea Shewanella and Pseudomonas.

Two cytochromes c5 (SBcytc and SVcytc) have been derived from Shewanella living in the deep-sea, which is a high pressure environment, so it could be that these proteins are more stable at high pressure than at atmospheric pressure, 0.1 MPa. This study, however, revealed that SBcytc and SVcytc were more stable at 0.1 MPa than at higher pressure. In addition, at 0.1-150 MPa, the stability of SBcytc and SVcytc was higher than that of homologues from atmospheric-pressure Shewanella, which was due to hydrogen bond formation with the heme in the former two proteins. This study further revealed that cytochrome c551 (PMcytc) of deep-sea Pseudomonas was more stable than a homologue of atmospheric-pressure Pseudomonas aeruginosa, and that specific hydrogen bond formation with the heme also occurred in the former. Although SBcytc and SVcytc, and PMcytc are phylogenetically very distant, these deep-sea cytochromes c are commonly stabilized through hydrogen bond formation.

Pseudomonas aeruginosa cytochrome c551 denaturation by five systematic urea derivatives that differ in the alkyl chain length.

Reversible denaturation of Pseudomonas aeruginosa cytochrome c551 (PAc551) could be followed using five systematic urea derivatives that differ in the alkyl chain length, i.e. urea, N-methylurea (MU), N-ethylurea (EU), N-propylurea (PU), and N-butylurea (BU). The BU concentration was the lowest required for the PAc551 denaturation, those of PU, EU, MU, and urea being gradually higher. Furthermore, the accessible surface area difference upon PAc551 denaturation caused by BU was found to be the highest, those by PU, EU, MU, and urea being gradually lower. These findings indicate that urea derivatives with longer alkyl chains are stronger denaturants. In this study, as many as five systematic urea derivatives could be applied for the reversible denaturation of a single protein, PAc551, for the first time, and the effects of the alkyl chain length on protein denaturation were systematically verified by means of thermodynamic parameters.

Inhibition by all-trans retinoic acid of collagen degradation mediated by corneal fibroblasts.

BACKGROUND: We examined the effect of all-trans retinoic acid on collagen degradation mediated by corneal fibroblasts. METHODS: Rabbit corneal fibroblasts were cultured with or without all-trans retinoic acid in a three-dimensional collagen gel, and the extent of collagen degradation was determined by measurement of hydroxyproline in acid hydrolysates of culture supernatants. Matrix metalloproteinase expression was examined by immunoblot analysis and gelatin zymography. The abundance and phosphorylation state of the endogenous nuclear factor-kappaB inhibitor IκB-α were examined by immunoblot analysis. Corneal ulceration was induced by injection of lipopolysaccharide into the central corneal stroma of rabbits and was assessed by observation with a slitlamp microscope. RESULTS: All-trans retinoic acid inhibited interleukin-1ß-induced collagen degradation by corneal fibroblasts in a concentration- and time-dependent manner. It also attenuated the release and activation of matrix metalloproteinases as well as the phosphorylation and degradation of IκB-α induced by interleukin-1ß in these cells. Topical application of all-trans retinoic acid suppressed corneal ulceration induced by injection of lipopolysaccharide into the corneal stroma. CONCLUSIONS: All-trans retinoic acid inhibited collagen degradation mediated by corneal fibroblasts exposed to interleukin-1ß, with this effect being accompanied by suppression of nuclear factor-kappaB signalling as well as of matrix metalloproteinase release and activation in these cells. All-trans retinoic acid also attenuated lipopolysaccharide-induced corneal ulceration in vivo. Our results therefore suggest that all-trans retinoic acid might prove effective for the treatment of patients with corneal ulceration.

A phase I study of split-dose cisplatin and etoposide with concurrent accelerated hyperfractionated thoracic radiotherapy in elderly patients with limited-disease small cell lung cancer.

OBJECTIVE: The optimal treatment for elderly patients with limited-disease small cell lung cancer has not been defined. We therefore performed a Phase I study for split-dose cisplatin plus etoposide combined with early concurrent accelerated hyperfractionated thoracic radiotherapy in elderly (70 years of age or older) patients with limited-disease small cell lung cancer. METHODS: Chemotherapy consisted of cisplatin at 20 or 25 mg/m(2) and etoposide at 80 mg/m(2), both administered on Days 1-3 of a 28-day cycle. Radiotherapy was initiated at the onset of chemotherapy and administered at a dose of 1.5 Gy twice daily over 3 weeks up to a total dose of 45 Gy. RESULTS: Twelve patients with a median age of 76 years (range, 70-85) were enrolled. Dose-limiting toxicities occurred in two (hyponatremia of Grade 4 or cardiac ischemia of Grade 3) of the six patients treated at dose Level 1 as well as in three (perforation of the sigmoid colon of Grade 3, febrile neutropenia of Grade 3, or hyponatremia of Grade 3) of the six patients treated at dose Level 2. The most frequent non-hematologic adverse events included anorexia, fatigue, esophagitis and pneumonitis, but most of these events were of Grade 1 or 2. CONCLUSIONS: The recommended dose for cisplatin and etoposide chemotherapy administered on Days 1-3 was determined to be 20 and 80 mg/m(2), respectively. Our results indicate that split-dose cisplatin plus etoposide chemotherapy combined with early concurrent accelerated hyperfractionated thoracic radiotherapy is well tolerated by elderly patients with limited-disease small cell lung cancer. CLINICAL TRIALS REGISTRATION NO: UMIN Clinical Trials Registry (UMIN-CTR) C000000143.

[Contribution of increasing age to carotid plaque morphology and symptoms].

OBJECTIVE: Aging is considered to cause atherosclerotic changes in the carotid artery, but few studies have evaluated this relationship. In this study, we used carotid plaques removed from patients with carotid artery stenosis and investigated how aging contributes to carotid plaque morphology and symptoms. MATERIALS AND METHODS: A total of 60 patients(55 men, 5 women; mean age, 70.5 years; range, 53-85 years) treated at our hospital between January 2009 and April 2012 were enrolled in this study. All patients underwent carotid endarterectomy; their carotid plaques were stained with hematoxylin-eosin and/or Elastica-Masson stain and examined by a pathologist. Using these data, the carotid systolic velocity and plaque morphology were analyzed considering the age by decade as well as the symptomatology. RESULTS: Of the 60 patients, 29 were symptomatic(transient ischemic attack (TIA) in 8 patients; infarction in 20;and amaurosis in 1). Symptoms were less common as patient age increased. The incidence of TIA also tended to decrease with an increase in age, although the opposite trend was seen with infarction. In plaque morphology, the presence of active plaque, macrophage, inflammatory infiltration, and capillary angiogenesis decreased as age increased, while the presence of degenerative plaques, decrease in smooth muscle cell number, and calcification inversely increased. Active, degenerative, and combined (active/degenerative) lesions are statistically unrelated to symptoms as well as systolic velocity (cm/sec) at the carotid stenosis. The rates of hemorrhagic lesions were similar among decades, but the lesion statistically contributed to increasing symptoms (p=0.0045) and increasing systolic velocity (p=0.031). CONCLUSION: Increasing age contributes to morphological changes in carotid plaques and symptoms. When hemorrhagic lesions are suspected in carotid plaques, patients will be symptomatic and may require surgery.

Association of resting energy expenditure with phase angle in hospitalized older patients: a cross-sectional analysis.

BACKGROUND/OBJECTIVES: Resting energy expenditure (REE) constitutes the largest component of total energy expenditure and undergoes an age-related decline that is unexplained by decreased fat-free mass. Phase angle (PhA) is a cellular health indicator that is possibly associated with REE. We investigated the association of REE and PhA in hospitalized older adults. SUBJECTS/METHODS: This single-center, cross-sectional analysis utilized the baseline data from a prospective longitudinal study and included 131 eligible patients aged ≥70 years. The REE was measured using indirect calorimetry, and PhA and body composition were assessed using bioelectrical impedance. The association between REE, PhA, and body composition was examined, and REE was compared using previously reported PhA cutoff values. RESULTS: In this cohort with a mean (±standard deviation) age of 87.4 (±7.0) years, 34.4% of the participants were men. REE and PhA correlated strongly (r: 0.562, p < 0.001) and significantly after adjusting for age and sex (r: 0.433, p < 0.001). Multivariate analysis showed a significant independent association between REE and PhA and skeletal muscle mass (standardized ß [95% CI]; 28.072 [2.188-53.956], p = 0.035) without any significant interaction between PhA and age on REE. The low PhA group had a significantly lower REE (kcal/day; 890 [856-925] vs. 1077 [1033-1122], p < 0.001), and this remained significant after adjusting for age, sex, and skeletal muscle mass index. CONCLUSIONS: PhA is associated with REE in older adults. Adjusting REE calculation algorithms based on PhA values and correcting predicted REE according to PhA may aid in determining more accurate energy requirements.

Comparison of efficacy and safety of 1- and 3-month luteinizing hormone-releasing hormone agonist depots as initial therapies for prostate cancer.

BACKGROUND: We compared the efficacy and safety of 1- and 3-month depots of the luteinizing hormone-releasing hormone (LH-RH) agonist goserelin acetate in prostate cancer patients. METHODS: Patients were randomly assigned to the Direct Group that received the goserelin 3-month depot or the Switch Group that began with the 1-month depot for the first 3 months and then switched to the 3-month depot. All patients were co-administered the antiandrogen agent bicalutamide. Serum testosterone and prostate-specific antigen (PSA) levels and adverse events were recorded at weeks 4, 8, 12, and 24. RESULTS: Baseline testosterone levels in the Direct and Switch Groups were 4.98 and 5.07 ng/mL, respectively (P = 0.798). At each week, the levels in both groups were ≤0.50 ng/mL (castration level) with no significant differences between them. All of the patients in the Switch Group and 98.1 % in the Direct Group had achieved castration levels at week 12, and 100 % had achieved such levels at week 24. Baseline PSA levels in the Direct and Switch Groups were 52.37 and 46.72 ng/mL, respectively (P = 0.793). Levels in both groups dropped continuously, to about 1.0 ng/mL at week 24, with no significant differences between the groups at any time. Three patients in the Direct Group experienced adverse events that were attributed to the co-administered bicalutamide. CONCLUSIONS: There was no difference in the efficacy or safety between the 1- and 3-month depots of goserelin when given as initial prostate cancer treatment in combination with bicalutamide. Patients must be monitored for adverse events associated with bicalutamide.

[Intrathoracic washing with urokinase was effective for empyema with atelectasis].

A 60-year-old man had a medical examination because of fever in the emergency hospital and had a diagnosis of pneumonia and was treated, but he was admitted to our hospital 2 days later because there was not the improvement of his symptom. The chest computed tomography(CT)image showed multilocular pleural effusions and lower lobe atelectasis with the air bronchogram on the left side. We diagnosed the case as empyema and inserted a catheter, but drainage was very few and injected 60,000 urokinase units for 3 days from the next day. We removed a drain 2 days after the 3rd infusion, and the pleural thickening became mild, and atelectasis was gradually improved in the chest CT image, and the inflammatory reaction was reduced, too. The intrathoracic washing with urokinase was thought to be effective for empyema with atelectasis.

Patient with Adult T-cell Leukemia and Lung Infection caused by Mycobacterium abscessus: Successful Treatment with Intensive Chemotherapy Followed by Haploidentical Hematopoietic Stem Cell Transplantation: A Case Report.

A 63-year-old woman with adult T-cell leukemia (ATL) lymphomatous type developed a mild dry cough. Computed tomography revealed lung lesions with a tree-in-bud appearance during intensive chemotherapy. Antibodies against Mycobacterium avium complex were positive. Bronchoalveolar lavage culture showed growth of M. abscessus complex. Finally, M. abscessus subsp. massiliense was also identified. Sequential use of antimicrobials, including macrolides, was introduced during intensive chemotherapy, and the patient successfully underwent allogeneic hematopoietic stem cell transplantation (AHSCT). This is the first case report of a patient with ATL complicated by M. massiliense lung infection, who was successfully treated with haploidentical AHSCT using various combinations of antimicrobials.

New prediction equations for resting energy expenditure in older hospitalized patients: Development and validation.

OBJECTIVES: Accurate resting energy expenditure (REE) prediction is needed to prevent over- or underfeeding in older hospitalized patients. However, few validated REE prediction Equations are known for such patients. Therefore, this study aimed to develop new REE prediction Equations and evaluate their validity. METHODS: This single-center, cross-sectional study enrolled 134 patients ages ≥70 y. For holdout validation, patients were randomized in a 3:1 ratio; for the development data set, a new Equation was developed according to the measured REE using indirect calorimetry. The new and existing Equations were compared using the validation data set. RESULTS: Mean patient age was 87.4 ± 6.9 y, and 34.3% were male. Two Equations were developed in multivariable regression models: Equation 1: REE (kcal/day) = 313.582 + Height (cm) × 3.973 + Body weight (kg) × 5.332 - Age (y) × 5.474 - (0 if male; 1 if female) × 20.012 + Calf circumference (cm) × 12.174; and Equation 2: REE (kcal/day) = 594.819 + Height (cm) × 3.760 + Body weight (kg) × 8.888 - Age (y) × 6.298 - (0 if male; 1 if female) × 16.396. The mean relative bias (95% CI) with measured REE as a reference had a small bias for Equations 1 and 2 (-0.1 [-4.1 to 3.9]% and -0.2 [-4.4 to 4.1]%, respectively); however, the Harris-Benedict, Food and Agriculture Organization of the United Nations/World Health Organization/United Nations University, Ganpule, and body weight × 20 Equations had larger biases (-6.2 [-10.3 to -2.0]%; 5.3 [1.3 to 9.3]%; -13.9 [-18.6 to -9.3]%; and -11.6 [-16.1 to -7.1]%, respectively). CONCLUSIONS: New prediction Equations using height, body weight, age, sex, and calf circumference improve REE prediction accuracy in older hospitalized patients.

Detrusor-Overactivity-Related Voiding in Women Mimics Bladder Outflow Obstruction and Conceals Underactivity.

OBJECTIVE: Urodynamics of the storage phase showing detrusor overactivity is com- mon in neurogenic bladder patients. Terminal detrusor overactivity, which is defined by involuntary detrusor contraction that cannot be inhibited, causes urinary incon- tinence. Such incontinence causes a unique voiding in neurogenic bladder patients. During the voiding phase, the detrusor pressure at Qmax (Pdet.Qmax)/maximum flow rate (Qmax) (P/Q) is the gold standard for differentiating between detrusor underactiv- ity and bladder outflow obstruction. We investigated whether a valid identification of lower urinary tract dysfunction could be established from P/Q assessment of detrusor overactivity-related voiding patients. METHODS: This study evaluated 2 types of voiding. Detrusor overactivity-related void- ing is involuntary detrusor contraction that results in micturition or voiding after per- mission to void when detrusor overactivity has occurred, while voluntary voiding is voiding voluntarily after permission to void and without terminal detrusor overactivity. We evaluated female patients with neurogenic bladder who could undergo micturition without catheterization. A pressure flow study compared the 2 groups. RESULTS: Comparison of the detrusor overactivity-related voiding group (n=20) and the voluntary voiding group (n=12) found statistically significant differences with a lower Qmax and higher Pdet.Qmax (P=.01) in the detrusor overactivity-related void- ing group. The linear regression analysis P/Q plot showed the positivity and negativity value of the slope that was reversed in the 2 groups (-0.089 vs. 0.198). CONCLUSION: Current results showed different P/Q plot patterns between 2 types of voiding in patients with neurogenic bladder. These findings suggest there is increased detrusor pressure observed in detrusor overactivity-related voiding that mimics out- flow obstruction.

Characterization of cultivated murine lacrimal gland epithelial cells.

PURPOSE: To date, mouse lacrimal gland epithelial cells have been cultured successfully but only in cases involving newborn mouse lacrimal glands. In this work, we attempted to cultivate and characterize adult mouse lacrimal gland epithelial cells. METHODS: Lacrimal glands were removed from newborn mice (C57B/6) and isolated lacrimal gland epithelial cells were seeded onto tissue culture treated or low adherent culture dishes in Cnt-07 culture medium with or without cholera toxin. Cultivated cells were characterized by immunostaining with pan-cytokeratin, α-smooth muscle actin, and lactoferrin antibodies. Lacrimal gland cells from 7-week-old green fluorescent protein (GFP) and non-GFP (C57B/6) mice were mixed and seeded onto uncoated dishes to assess sphere-forming efficiency. Cells were also seeded onto 3T3 cell feeder layers to assess colony forming efficiency. RESULTS: Lacrimal gland epithelial cells were selectively cultured with cholera toxin, and cell type was verified by pan-cytokeratin and α-smooth muscle actin immunostaining. Sphere formation from single cells of adult mice was observed using specific medium and low adherent culture dishes. These cells could also undergo colony formation on 3T3 feeder cells. CONCLUSIONS: Adult mouse lacrimal gland epithelial cells were successfully cultivated in cholera toxin-containing medium, and were observed to form spheres from single cells.

Effect of Ankle Weights as a Frailty Prevention Strategy in the Community-Dwelling Elderly: A Preliminary Report.

Since the start of the COVID-19 pandemic, many healthy older adults have been less willing to engage in group exercise for fear of contracting this illness. Therefore, there is a need for an effective home-based exercise program to prevent frailty in the elderly. In this study, we assessed the effectiveness of ankle weights as a frailty prevention device for older adults. The study participants were aged 50−90 years and were screened for falls using the Motor Fitness Scale. Participants were divided into two age groups (≤70 and >70 years) for analysis. Older community-dwelling adults were invited to use ankle weights for 3 months. Seventy-four people responded to the invitation. Physical and cognitive status and performance (body composition, grip strength, standing on one leg with eyes open, the 30 s chair stand test (CS-30), Timed Up and Go test, walking speed, body sway, Japanese version of the Montreal Cognitive Assessment) were assessed before and after 3 months of intervention. CS-30 performance improved during the study. CS-30 reflects lower limb/trunk muscle strength and can be used to indicate the risk of falls. Wearing ankle weights can be recommended for strengthening the muscles of the lower limb and trunk in the elderly.

Cohort profile: Alliance for Quality Assessment in Healthcare-Dialysis (AQuAH-D) prospective cohort study of patients on haemodialysis in Japan.

PURPOSE: The global burden of kidney failure is increasing, but the treatment of kidney failure varies widely between patients, between dialysis facilities and over time. The Alliance for Quality Assessment in Healthcare-Dialysis (AQuAH-D) aims to conduct efficient and timely cohort studies on associations between those variations and clinical and patient-reported outcomes. PARTICIPANTS: Included are outpatients aged 20 years old or older who are undergoing haemodialysis and have consented to participate. A total of 2895 patients were enrolled from 25 facilities in Japan between August 2018 and July 2020 and are to be followed until 31 December 2026. Chart review and annual questionnaires are used to collect data on patient characteristics and on outcomes including quality of life. Data on medications, haemodialysis prescriptions and blood tests are obtained from existing electronic records. Data are collected retrospectively from 1 January 2017 to patient enrolment, and prospectively from patient enrolment until the end of December 2026. FINDINGS TO DATE: To date, the mean age is 68.3 (SD 12.2) years and 35.2% are female. The most common cause of kidney failure is diabetic nephropathy (37.4%). In January 2020, the facilities' median weekly doses of erythropoietin stimulating agent (ESA) and of intravenous vitamin D ranged from 1846 to 9692 IU (epoetin alfa equivalent) and 0.78 to 2.25 µg (calcitriol equivalent), respectively. The facilities' percentages of patients to whom calcimimetics are prescribed varied from 19% to 79%. During the retrospective period (averaging 1.85 years per participant), the incidence rates of any hospitalisation and of hospitalisation due to cardiovascular disease were 67.2 and 12.0 per 100 person-years, respectively. FUTURE PLANS: AQuAH-D data will be updated every 6 months and will be available for studies addressing a wide range of research questions, using the advantages of granular data and quality-of-life measurement of ageing patients on haemodialysis.

Resting Energy Expenditure in Older Inpatients: A Comparison of Prediction Equations and Measurements.

Determining energy requirements are an important component of nutritional support for patients with malnutrition; however, the validity of prediction equations for resting energy expenditure (REE) is disputed in older hospitalized patients. We aimed to assess the validity of these equations in older hospitalized patients in Japan. This was a single-center, cross-sectional study of 100 patients aged ≥70 years, hospitalized between January 2020 and December 2021. REE was measured using an indirect calorimeter and was compared to the predicted values calculated from five REE prediction equations. The mean (95% confidence interval) measured REE was 968.1 (931.0, 1005.3) kcal/day, and the mean predicted REE was higher for the FAO/WHO/UNU (1014.3 [987.1, 1041.6] kcal/day, p = 0.164) and Schofield (1066.0 [1045.8, 1086.2] kcal/day, p < 0.001) equations and lower for the Harris-Benedict (898.6 [873.1, 924.1] kcal/day, p = 0.011), Ganpule (830.1 [790.3, 869.9] kcal/day, p < 0.001), and body weight (kg) × 20 (857.7 [821.9, 893.5] kcal/day, p < 0.001) equations. In the age group analysis, none of the predicted values were within a 10% error for more than 80% of patients aged 70−89 years and ≥90 years. The five REE prediction equations did not provide accurate estimates. Validated REE prediction equations need to be developed for older hospitalized patients.