Search

We report the case of a 66-year-old man diagnosed with multiple pulmonary angiosarcomas 4 years post-endovascular aneurysm repair (EVAR). The patient was healthy with a good postoperative course, besides requiring additional coil embolization for a lumbar artery type 2 endoleak (T2EL) 3 years post-EVAR. He presented to the emergency department with sudden respiratory distress and severe anemia. Computed tomography (CT) revealed multiple pulmonary nodules bilaterally. Thoracoscopic pulmonary nodule resection and pathological examination revealed angiosarcoma. The condition progressed rapidly, and the patient died 17 days post-admission. Postmortem pathological analysis demonstrated angiosarcomas of the primary residual aneurysmal mass post-EVAR, inferior vena cava invasion adjacent to the mass, and multiple pulmonary metastases bilaterally. Findings suggestive of angiosarcoma were found 6 months post-T2EL coil embolization when reviewing the annual positron emission tomography CT. We suspect that irradiation during T2EL treatment post-EVAR may have triggered angiosarcoma development. To the best of our knowledge, this is the first study to evaluate the relationship between T2EL and angiosarcoma.

Abstract Background Implant impingement and soft tissue tension are factors involved in dislocation after total hip arthroplasty (THA). Combined anteversion (CA) has been used as an indicator for implant placement. However, optimal implant placement remains a challenge. Moreover, the effect of changes in offset on dislocation is still unclear. In this study, we aimed to clarify the effects of postoperative CA and pre- and postoperative changes in offset on dislocation. Methods Included were patients who underwent primary cementless THA between 2013 and 2020. The mean values of CA and offset in the dislocation and non-dislocation groups were compared. The CA values within ± 10% of the recommended values were defined as good CA, and those outside the range were rated as poor CA. The dislocation rates were compared between the good and poor CA groups and between the groups with and without increased offset. Results A total of 283 hips were included. The mean values of CA in the dislocation and non-dislocation groups were significantly different (P

In this study, an ensemble inflow-prediction system was developed for a hydropower-generation dam in the upper Sai River basin, and the accuracy of ensemble inflow prediction, which is important for efficient dam operation, was investigated. First, the Water and Energy Based Distributed Hydrological Model for Snow (WEB-DHM-S), a hydrological model developed for the Sai River basin, can represent the hydrological process from warm to cold seasons. Next, a system was developed on the Data Integration and Analysis System (DIAS) to predict inflows into the dam by inputting real-time meteorological data and ensemble rainfall forecast data into WEB-DHM-S. The WEB-DHM-S was calibrated and validated over a 3-year period from August 2015 to July 2018, and showed good agreement with observed inflows from base flow to peak flow and snowmelt runoff in each year. The results of inflow forecasting during frontal rainfall in August 2021 by inputting ensemble rainfall forecasts up to 39 h ahead showed that at the Inekoki Dam site, the total inflow (volume) to the peak was predicted with an accuracy of within 20% at 30 h, 24 h, 18 h, 12 h, and 6 h before the peak. These ensemble inflow forecasts can help optimize dam operations.

Abstract The post-surgical fluid leakage from the tubular tissues is a critical symptom after gastrointestinal or urinary tract surgeries. Elucidating the mechanism for such abnormalities is vital in surgical and medical science. The exposure of the fluid such as peritonitis due to urinary or gastrointestinal perforation has been reported to induce severe inflammation to the surrounding tissue. However, there have been no reports for the tissue responses by fluid extravasation and assessment of post-surgical and injury complication processes is therefore vital. The current model mouse study aims to investigate the effect of the urinary extravasation of the urethral injuries. Analyses on the urinary extravasation affecting both urethral mesenchyme and epithelium and the resultant spongio-fibrosis/urethral stricture were performed. The urine was injected from the lumen of urethra exposing the surrounding mesenchyme after the injury. The wound healing responses with urinary extravasation were shown as severe edematous mesenchymal lesions with the narrow urethral lumen. The epithelial cell proliferation was significantly increased in the wide layers. The mesenchymal spongio-fibrosis was induced by urethral injury with subsequent extravasation. The current report thus offers a novel research tool for surgical sciences on the urinary tract.

Abstract Background Obtaining a larger theoretical range of motion (ROM) is crucial to avoid prosthetic impingement after total hip arthroplasty (THA); however, no reports have examined the permissible range values of combined anteversion (CA) satisfying targeted ROM without prosthetic impingement. This retrospective study aimed to evaluate the possible postoperative CA extent that would allow meeting target ROM criteria according to Yoshimine’s theory using computed tomography (CT)-based three-dimensional motion analysis after THA. Methods This study included 114 patients (133 hips) who underwent cementless primary THA using a CT-based navigation system and implants (oscillation angle ≥ 135°). Implant positions were determined using Yoshimine's CA formula. Postoperative evaluation was conducted using a three-dimensional templating software for CT data. The postoperative Yoshimine’s and Widmer’s CA was calculated, and the difference between the target and postoperative values was defined as the error of Yoshimine’s CA and Widmer’s CA. Prosthetic ROM was assessed by Yoshimine’s stringent criteria for activities of daily living. Based on fulfilling these criteria, all patients were divided into the ROM (+) and ROM (−) groups. Evaluation items were compared between the two groups. Results There were 111 and 22 hips in the ROM (+) and ROM (−) groups, respectively. A significant difference was noted in the absolute error of Yoshimine’s and Widmer’s CA between the two groups. Using receiver operating characteristic analysis, threshold values of 6.0 (higher values indicate greater disability; sensitivity 90.9%, specificity 72.1%) for the absolute Yoshimine’s CA difference (area under the curve [AUC] 0.87, P

Abstract An 88-year-old man had intermittent claudication of his right leg. Angiography revealed severely calcified plaque in the common femoral artery. Endovascular treatment was performed by contralateral approach. We attempted to penetrate the center of the calcified plaque and perform balloon dilatation. However, a 0.014-inch stiff guidewire could not enter the center of the lesion. Thus, we used an inner cylinder of 15-cm 20G long needle directly through the retrograde femoral sheath and successfully introduced the guidewire into the calcified plaque. Crosser and balloon dilatation resulted in 50 % stenosis. To cross the center of calcified plaque, it is important to obtain sufficient lumen gain at the non-stenting zone.

Abstract Background Currently, the success rate of EVT for treating CTO of the SFA is high; however, EVT is still found to be insufficient in treating CTOs with severely calcified lesions. Even if the guidewire crosses the lesion, the calcifications may still cause difficulties during stent expansion. Main text A 78-year-old male had been reported to have intermittent claudication with chronic total occlusion (CTO) of the right superficial femoral artery (SFA). Angiography revealed severely calcified plaque (Angiographic calcium score: Group4a [1]) at the ostium of the SFA. Stenting posed a risk of underexpansion, causing the plaque to shift to the deep femoral artery. we decided to remove the calcified plaque using biopsy forceps. After removing the extended calcified plaque, the guidewire could cross easily, and the self-expandable stent was well dilated without causing the plaque to shift to the DFA. Conclusions Biopsy forceps may be used in some endovascular cases to remove severely calcified lesions. To ensure the safety of the patient, the physician must be adept at performing this technique before attempting it.

We report a case of a girl with inverted papilloma of the urinary bladder, which was detected by ultrasonographic screening based on the findings of a school medical checkup. The case was an 11-year-old girl. She was diagnosed as having occult hematuria and proteinuria by a school medical checkup. Abdominal ultrasonography revealed a high echoic lesion protruding into the bladder. Cystoscopic findings showed a thumb fingertip-sized papillary pedunculated tumor located at the trigone in the bladder. Transurethral resection was performed and pathological examination rendered the diagnosis of inverted papilloma of the urinary bladder. Eight cases of bladder inverted papilloma in children have been reported including our case. This is the first case detected asymptomatically based on a school medical checkup. We believe that ultrasound screening of the urinary tract should be considered when treating patients with positive occult hematuria, such as in a school medical checkup.

Abstract The incidence of dry eye disease is increasing worldwide because of the aging population and increasing use of information technology. Dry eye disease manifests as tear-layer instability and inflammation caused by osmotic hypersensitization in tear fluids; however, to our knowledge, no agent that treats both pathologies simultaneously is available. Molecular hydrogen (H2) is known to be effective against various diseases; therefore, we aimed to elucidate the effects of H2 on tear dynamics and the treatment of dry eye disease. We revealed that administering a persistent H2-generating supplement increased the human exhaled H2 concentration (p

Abstract A decrease in the elasticity of the ocular lens during aging is associated with loss of the accommodative ability of the eye, leading to presbyopia. Although near vision impairment is a social issue affecting the length of healthy life expectancy and productivity of elderly people, an effective treatment to improve near vision has not yet become available. Here we examined the effect of Enterococcus faecium WB2000, Lactobacillus pentosus TJ515, and resveratrol on lens elasticity in rats, where the stiffness of the ocular lens increases exponentially during the aging process. A combination of WB2000 and resveratrol improved lens elasticity not only in the long term but also with just short-term treatment. In addition, TJ515 decreased stiffness in the eye lens with long-term treatment. Therefore, the oral administration of WB2000 and resveratrol or TJ515 may be a potential approach for managing the progression of near vision impairment.

Surgical training using live animals such as pigs is one of the best ways of achieving skilled techniques and fostering confidence in preclinical medical students and surgeon trainees. However, due to animal welfare ethics, laboratory animals’ usage for training should be kept to a minimum. We have developed a novel kidney organ model utilizing a simple procedure in which the kidney is first refluxed with N-vinyl-2-pyrrolidone (NVP) solution for 1 hour in its bath, followed by permeation for 23 hours, with a subsequent freshwater refluxed for 48 hours in the washing step. Surgical simulation of the prepared kidney model (NVP-fixed kidney) was compared with three types of other basic known simulation models (fresh kidney, freeze-thaw kidney, and FA-fixed kidney) by various evaluations. We found the NVP-fixed kidney to mimicked fresh kidney function the most, pertaining to the hardness, and strength of the renal parenchyma. Moreover, the NVP-fixed kidney demonstrated successful blood-like fluids perfusion and electrocautery. Further, we confirmed that surgical training could be performed under conditions closer to actual clinical practice. Our findings suggest that our model does not only contribute to improving surgical skills but also inspires the utilization of otherwise, discarded inedible livestock organs as models for surgical training.

This study characterized the effects of a deficiency of the hypoxia-responsive gene, differentiated embryonic chondrocyte gene 1 (Dec1), in attenuating the biological function of orthodontic tooth movement (OTM) and examined the roles of ribosomal proteins in the hypoxic environment during OTM. HIF-1α transgenic mice and control mice were used for hypoxic regulation of periodontal ligament (PDL) fibroblasts. Dec1 knockout (Dec1KO) and wild-type (WT) littermate C57BL/6 mice were used as in vivo models of OTM. The unstimulated contralateral side served as a control. In vitro, human PDL fibroblasts were exposed to compression forces for 2, 4, 6, 24, and 48 h. HIF-1α transgenic mice had high expression levels of Dec1, HSP105, and ribosomal proteins compared to control mice. The WT OTM mice displayed increased Dec1 expression in the PDL fibroblasts. Micro-CT analysis showed slower OTM in Dec1KO mice compared to WT mice. Increased immunostaining of ribosomal proteins was observed in WT OTM mice compared to Dec1KO OTM mice. Under hypoxia, Dec1 knockdown caused a significant suppression of ribosomal protein expression in PDL fibroblasts. These results reveal that the hypoxic environment in OTM could have implications for the functions of Dec1 and ribosomal proteins to rejuvenate periodontal tissue homeostasis.

Abstract Background Data are still lacking regarding the effects of minimally interrupted direct oral anticoagulants (MID) on the intensity of intraprocedural anticoagulation of atrial fibrillation (AF) ablation. Methods A total of consecutive 269 patients who undergone AF ablation were eligible for the study. All oral anticoagulants (OACs) were discontinued just one dose before the procedure except warfarin. We assessed the total required dose of UFH and time‐to‐target ACT > 300 seconds (TTA) for each of direct oral anticoagulant (DOAC) groups compared with the uninterrupted warfarin group. Results DOACs were used in 86% of the patients in the present study (dabigatran group (DG)‐17%, rivaroxaban group (RG)‐30%, apixaban group (AG)‐29%, and edoxaban group (EG)‐10%). DG and EG used comparable dose of total UFH to WG (WG vs DG; 206 ± 53 U/kg vs 231 ± 63 U/kg; P = .664, vs EG; 239 ± 67 U/kg; P = .335), while RG and AG required higher total UFH (WG vs RG; 206 ± 53 U/kg vs 270 ± 63 U/kg; P 75 years, and body weight

Background and Objectives: Precise acetabular cup placement is essential for successful total hip arthroplasty (THA). In obese patients, its accuracy is often difficult to achieve because of the thickness of the soft tissues. This study aimed to determine the relationship between the accuracy of acetabular cup angle and body mass index (BMI) in posterolateral THA using the computed tomography-based navigation (CT-navi) system. Materials and Methods: We retrospectively reviewed 145 consecutive primary THAs using the CT-navi system between January 2015 and January 2018. All surgeries were performed using cementless cups employing the posterolateral approach with the patient in the decubitus position. We compared the radiographic inclination and anteversion obtained intraoperatively from the CT-navi with those measured by postoperative CT using three-dimensional templating software. We evaluated the relationship between the extent of errors and correlation with BMI. Results: In non-overweight patients (BMI < 25, 88 hips), the mean navigation errors for inclination were 2.8 ± 2.2° and for anteversion were 2.6 ± 2.3°. Meanwhile, in overweight patients (BMI ≥ 25, 57 hips), the mean navigation errors were 2.6 ± 2.4° for inclination and 2.4 ± 2.4° for anteversion. We found no significant difference between overweight and non-overweight patients in both inclination and anteversion. There was no correlation between the extent of errors and BMI. Conclusions: In posterolateral THA, CT-navi can aid the precise placement of the acetabular cup irrespective of a patient’s BMI.

Background Dialysis is an independent risk factor for in‐stent restenosis (ISR) after stent implantation in coronary arteries. However, the characteristics of ISR in patients undergoing dialysis remain unclear, as there are no histological studies evaluating the causes of this condition. The aim of the present study was to investigate the causes of ISR between patients who are undergoing dialysis and those who are not by evaluating tissues obtained from ISR lesions using directional coronary atherectomy. Methods and Results A total of 29 ISR lesions from 29 patients included in a multicenter directional coronary atherectomy registry of 128 patients were selected for analysis and divided into a dialysis group (n=8) and a nondialysis group (n=21). Histopathological evaluation demonstrated that an in‐stent calcified nodule was a major histological characteristic of ISR lesions in the dialysis group and the prevalence of an in‐stent calcified nodule was significantly higher in the dialysis group compared with the nondialysis group (75% versus 5%, respectively; P

Food crises caused by growing global population or environmental changes are predicted in the near future; therefore, sustainable solutions are needed. Edible insects, which are rich in protein and can save feed and environmental resources, have the potential to be a sustainable alternative protein source. However, there is limited evidence on the impact on health. In this study, we investigated the biological effects of ingesting bee larva by examining their effects on amino acid, lipid, and glucose metabolism in animal models. In our animal experiments, the replacement of casein as a protein source, with edible insects, did not seem to cause any deficiency in murine amino acid levels in the plasma and liver. Metabolomic analysis of plasma metabolites showed decreased 3-methylhistidine and increased nicotinamide in the bee larva-derived protein-fed mice. Decreased levels of plasma 3-metylhistidine, an indicator of muscle degradation, implies that replacement to bee-larva protein from casein did not cause muscle degradation in vivo. We further investigated effects of increased plasma nicotinamide on peripheral tissue and found an increase in expression levels of genes involved in glucose uptake in muscle and thermogenesis in adipose tissue. These data imply that bee larva is a potential sustainable, safe and healthy alternative protein source.

Lactoferrin is a glycoprotein found at high concentrations within exocrine secretions, including tears. Low levels of lactoferrin have been implicated in the loss of tear secretion and ageing. Furthermore, lactoferrin possesses a range of functionalities, including anti-inflammatory properties and the ability to modulate the gut microbiota. Expanding evidence demonstrates a crucial role of the gut microbiota in immune regulation and development. The specific composition of bacterial species of the gut has a profound influence on local and systemic inflammation, leading to a protective capacity against a number of inflammatory diseases, potentially by the induction of regulatory immune cells. In this study, we demonstrated that oral administration of lactoferrin maintains tear secretion in a restraint and desiccating stress induced mouse model of dry eye disease. Furthermore, we revealed that lactoferrin induces the reduction of inflammatory cytokines, modulates gut microbiota, and induces short-chain fatty acid production. Whereas, the antibiotic vancomycin abrogates the effects of lactoferrin on dry eye disease and significantly reduces short-chain fatty acid concentrations. Therefore, this protective effect of LF against a mice model of DED may be explained by our observations of an altered gut microbiota and an enhanced production of immunomodulatory short-chain fatty acids.

Dry eye is a multifactorial disease characterized by ocular discomfort and visual impairment. Our previous studies have shown that royal jelly (RJ) has restored the capacity for tear secretion by modulating muscarinic calcium signaling. RJ contains acetylcholine, which is a major cholinergic neurotransmitter, and a unique set of fatty acids with C 8 to 12 chains, which are expected to be associated with health benefits. The purpose of the present study was to investigate the active components involved in tear secretion capacity, focusing on acetylcholine and fatty acids in RJ. Using the stress-induced dry-eye model mice, it was confirmed that acetylcholine with three fatty acids (10-hydroxydecanoic acid, 8-hydroxyoctanoic acid, and (R)-3,10-dihydroxydecanoic acid) was essential for tear secretion. In ex vivo Ca2+ imaging, these three fatty acids suppressed the decrease in intracellular modulation of Ca2+ in the lacrimal gland by acetylcholine when treated with acetylcholinesterase, indicating that the specific type of RJ fatty acids contributed to the stability of acetylcholine. To our knowledge, this study is the first to confirm that a specific compound combination is important for the pharmacological activities of RJ. Our results elucidate the active molecules and efficacy mechanisms of RJ.

Hydrogen gas (H2) reacts with strong oxidants, and the effectiveness of H2 inhalation or ingestion of H2 water has been demonstrated for many diseases. H2 produced by the intestinal microbiome from indigestible components is the major source of exogenous H2. In this study, we screened a wide variety of indigestible components that induce H2 production by the intestinal microbiome, which exhibits large diversity, and developed a beverage composed of cows’ milk with galactooligosaccharide, maltitol, and glucomannan (H2-producing milk). In clinical trials, the breath H2 concentration of most volunteers was increased by consumption of H2-producing milk 1 (each material: 1%) and H2-producing milk 2 (galactooligosaccharide: 1.5%, maltitol: 1%, and glucomannan: 0.1%). The total range of H2 production (area under the curve) increased and a higher peak concentration was observed compared with consumption of H2 water or pure cows’ milk. Thus, this material may be a desirable functional milk.

Abstract Tears are extracellular fluid secreted from the lacrimal gland (LG). Tears consist of a dynamic tri-layered film composed of secretions from the LG, Meibomian gland, and conjunctival goblet cells. The LG secretes the aqueous component of the tear, the Meibomian gland secretes the lipid component, and conjunctival goblet cells secrete mucin. The regulation of LG activity via the autonomic nervous system has been recognized as fundamental to maintaining aqueous tear flow. Here, we describe the role of a hormone, peripheral serotonin, in tear secretion. We found that blood serotonin concentration, changed by feeding a diet deprived of the serotonin precursor tryptophan, correlated with tear secretion, and that a sustained decrease in serotonin resulted in LG atrophy and autophagy. The combination of a decrease in serotonin with the interruption of autonomic neural stimuli to the LG preceded these alterations. Furthermore, we found that the serotonin type 3a receptor expressed in LG acinar cells is involved in tear secretion via intracellular calcium mobilization. Our findings demonstrate that hormonal regulation by serotonin, in cooperation with the autonomic nervous system, regulates tear secretion.

A 9-year-old girl was diagnosed with primary alveolar soft part sarcoma of the bladder after imaging examinations and transurethral resection (TUR) of the bladder tumor. As a positive surgical margin of the TUR indicated residual tumor cells, we performed a cystourethrectomy to remove the tumor. A continent urinary reservoir for self-catheterization was constructed using the Mainz pouch technique, and an abdominal (umbilical) continent catheterizable stoma using the appendix was performed. For 2.5 years postoperatively, the patient remained free of local recurrence and distant metastasis. The patient’s clinical course has been favorable, with good management of clean intermittent self-catheterization.

Covered cloacal exstrophy (CCE) is extremely rare condition. In patients with a single perineal orifice and no pubic bone separation, it is very difficult to suspect and/or diagnose CCE based on external signs alone. We present the case of a 2-month-old girl diagnosed with CCE based on cystography, ileostomy contrast study and cystoscopy.

Vesicoureteral reflux (VUR) is one of the most common diseases in pediatric urology and classified into primary and secondary VUR. Although posterior urethral valve (PUV) is well known as a cause of the secondary VUR, it is controversial that minor urethral deformity recognized in voiding cystourethrography represents mild end of PUV spectrum and contributes to the secondary VUR. We have been studying for these ten years congenital urethral obstructive lesions with special attention to its urethrographic and endoscopic morphology as well as therapeutic response with transurethral incision. Our conclusion to date is that congenital obstructive lesion in the postero-membranous urethra is exclusively PUV (types 1 and 3) and that severity of obstruction depends on broad spectrum of morphological features recognized in PUV. Endoscopic diagnostic criteria for PUV are being consolidated.

Dry eye is a multifactorial disease characterized by ocular discomfort and visual impairment. Lacrimal gland function has been shown to decrease with aging, a known potent risk factor for dry eye. We have previously found that orally administrated royal jelly (RJ) restored tear secretion in a rat model of dry eye.We examined the effects of RJ oral administration on dry eye in this prospective, randomized, double-blind, placebo-controlled study. Forty-three Japanese patients aged 20-60 years with subjective dry eye symptoms were randomized to an RJ group (1200 mg/tablet, six tablets daily) or a placebo group for 8 weeks. Keratoconjunctival epithelial damage, tear film break-up time, tear secretion volume, meibum grade, biochemical data, and subjective dry eye symptoms based on a questionnaire were investigated at baseline, and at 4 and 8 weeks after intervention. Adverse events were reported via medical interviews. In the RJ group, tear volume significantly increased after intervention (p = 0.0009). In particular, patients with a baseline Schirmer value of ≤10 mm showed a significant increase compared with baseline volume (p = 0.0005) and volume in the placebo group (p = 0.0051). No adverse events were reported. We also investigated the effect of RJ (300 mg/kg per day) administration using a mouse model of dry eye. Orally repeated administration of RJ preserved tear secretion, potentially through direct activation of the secretory function of the lacrimal glands.Our results suggest that RJ improves tear volume in patients with dry eye.Registered NO. the University Hospital Medical Information Network in Japan (UMIN000014446).

Dry eye disease is a disorder in tear film physiology, which leads to various abnormal states of ocular surface cells. In the present study, we evaluated the potential usefulness of orally applied maqui berry (Aristotelia chilensis) extract and the constituent anthocyanin as a preventative intervention in dry eye. Tear secretion capacity was evaluated following the oral administration of maqui berry extract to a rat blink-suppressed dry eye model. This suppressive effect of maqui berry extract and its constituent anthocyanins on reactive oxygen species formation from lacrimal gland was elevated by 2′, 7′-dichlorofluorescin diacetate. Maqui berry extract and delphinidin 3,5-O-diglucoside, an anthocyanin specifically contained in the maqui berry, suppressed reactive oxygen species formation from lacrimal gland tissue and preserved tear secretion. The result of the present study demonstrates that maqui berry extract can be used as a preventative intervention for dry eye by managing tear secretion capacity in the lacrimal gland.

Rebamipide ophthalmic solution is a mucin secretagogue which is an important therapeutic agent in the treatment of dry eye. It has been noted that dry eye in office workers is associated with a decrease in secretory mucin. This study aimed to evaluate the effects of 2% rebamipide ophthalmic solution in mice subjected to environmental dry eye stress (EDES), which mimics the conditions of office workers. Thirty eyes from thirty BALB/c mice (eight-week-old males) were divided into three treatment groups: artificial tear (vehicle), 2% rebamipide ophthalmic solution, and 0.1% hyaluronic acid (HA) ophthalmic solution. After four days of pretreatment, mice were exposed to EDES for three days. The corneal subbasal nerve and inflammatory cells were then examined using in vivo confocal microscopy. Following EDES exposure, the lissamine green staining score was significantly lower and corneal sensitivity was more preserved in the 2% rebamipide group than in the HA group. In addition, the subbasal nerve fiber density was significantly higher and the DC density was significantly lower in the 2% rebamipide group than in the HA group. Overall, the topical rebamipide ophthalmic solution showed more favorable therapeutic effects when compared to the HA ophthalmic solution in a mouse model of EDES, likely owing to its anti-inflammatory and neuroprotective effects.

MAMLD1 has been implicated in testicular function in both human and mouse fetuses. Although three patients with MAMLD1 mutations were reported to have hypergonadotropic hypogonadism in their teens, the functional significance of MAMLD1 in the postnatal testis remains unclear. Here, we analyzed the phenotype of Mamld1 knockout (KO) male mice at reproductive ages. The reproductive organs of KO male mice were morphologically unremarkable, except for relatively small testes. Seminiferous tubule size and number of proliferating spermatogonia/spermatocytes were reduced in the KO testis. Daily sperm production of KO mice was mildly attenuated, whereas total sperm counts in epididymal semen remained normal. Sperm motility and morphology, as well as androgen levels in serum and testicular tissues and the number of pups born from cross-mated wildtype (WT) female mice, were comparable between WT and KO male mice. These results indicate that MAMLD1 contributes to the maintenance of postnatal testicular growth and daily sperm production but is dispensable for androgen biosynthesis and fertility. MAMLD1 likely plays supporting roles in multiple and continuous steps of male reproduction.

Sea buckthorn (Hippophae rhamnoides)–derived products have traditionally been used as food and medicinal ingredients in Eastern countries. The purpose of this study was to investigate the effect of oral intake of sea buckthorn oil products on tear secretion using a murine dry eye model. Orally administered sea buckthorn pulp oil (not seed oil) restored aqueous tear secretion to its normal value under a dry eye condition. Palmitoleate (C16:1), a fatty acid present in sea buckthorn pulp oil, preserved tear secretion and suppressed inflammatory cytokines in the lacrimal gland to the same extent as that by pulp oil. These results suggest that an oral intake of sea buckthorn pulp oil has a potency to preserve tear secretion capacity in the dry eye state and palmitoleate, its main constituent fatty acid, is an active component of the oil. This effect may enable a potent diet-based treatment for the prevention of dry eye.

Tears are secreted from the lacrimal gland (LG), a dysfunction in which induces dry eye, resulting in ocular discomfort and visual impairment. Honey bee products are used as a nutritional source in daily life and medicine; however, little is known about their effects on dry eye. The aim of the present study was to investigate the effects of honey bee products on tear secretion capacity in dry eye. We selected raw honey, propolis, royal jelly (RJ), pollen, or larva from commercially available honey bee products. Tear secretion capacity was evaluated following the oral administration of each honey bee product in a rat blink-suppressed dry eye model. Changes in tear secretion, LG ATP content, and LG mitochondrial levels were measured. RJ restored the tear secretion capacity and decrease in LG ATP content and mitochondrial levels to the largest extent. Royal jelly can be used as a preventative intervention for dry eye by managing tear secretion capacity in the LG.

Chronic graft-versus-host disease (cGVHD), a serious complication following allogeneic HSCT (hematopoietic stem cell transplantation), is characterized by systemic fibrosis. The tissue renin-angiotensin system (RAS) is involved in the fibrotic pathogenesis, and an angiotensin II type 1 receptor (AT1R) antagonist can attenuate fibrosis. Tissue RAS is present in the lacrimal gland, lung, and liver, and is known to be involved in the fibrotic pathogenesis of the lung and liver. This study aimed to determine whether RAS is involved in fibrotic pathogenesis in the lacrimal gland and to assess the effect of an AT1R antagonist on preventing lacrimal gland, lung, and liver fibrosis in cGVHD model mice. We used the B10.D2→BALB/c (H-2(d)) MHC-compatible, multiple minor histocompatibility antigen-mismatched model, which reflects clinical and pathological symptoms of human cGVHD. First, we examined the localization and expression of RAS components in the lacrimal glands using immunohistochemistry and quantitative real-time polymerase chain reaction (PCR). Next, we administered an AT1R antagonist (valsartan; 10 mg/kg) or angiotensin II type 2 receptor (AT2R) antagonist (PD123319; 10 mg/kg) intraperitoneally into cGVHD model mice and assessed the fibrotic change in the lacrimal gland, lung, and liver. We demonstrated that fibroblasts expressed angiotensin II, AT1R, and AT2R, and that the mRNA expression of angiotensinogen was greater in the lacrimal glands of cGVHD model mice than in controls generated by syngeneic-HSCT. The inhibition experiment revealed that fibrosis of the lacrimal gland, lung, and liver was suppressed in mice treated with the AT1R antagonist, but not the AT2R antagonist. We conclude that RAS is involved in fibrotic pathogenesis in the lacrimal gland and that AT1R antagonist has a therapeutic effect on lacrimal gland, lung, and liver fibrosis in cGVHD model mice. Our findings point to AT1R antagonist as a possible target for therapeutic intervention in cGVHD.

Previous observations in a rat model of a non-Sjögren's syndrome (non-SS) type of dry eye seen in users of visual display terminals (VDT) indicated that secretory vesicle (SV) accumulation in the lacrimal gland epithelia contributes to the condition. Here, to examine this possibility in humans, we compared the lacrimal gland histology and percent SV area in the cytoplasm of acinar epithelial cells using light microscopy and transmission electron microscopy, in patients with VDT work-related non-SS dry-eye (VDT group), SS-induced dry-eye, and autopsied normal controls. In addition, the VAMP8 (vesicle-associated membrane protein 8, an exocrine-pathway molecule) and Rab3D (mature vesicle marker) were histochemically examined in lacrimal gland tissue sections. The lacrimal gland acini were larger in the VDT group than in the SS group, and the percent SV area was significantly higher in the VDT group than in the normal controls (P = 0.021) or SS group (P = 0.004). Immunostaining revealed abnormal distributions of VAMP8 in the VDT and SS groups. Rab3D was more strongly expressed in the cytoplasm of acinar epithelial cells in the VDT group than in that of normal controls. The duration of VDT use was significantly longer in the VDT group than in the other groups. These findings suggest that excessive SV accumulation in the acinar epithelia may contribute to the reduced tear secretion in VDT users.

Purpose. The Anatomic Fiber Metal plus stem (Zimmer) is one of the anatomically designed cementless stems to achieve stable fixation by metaphyseal fit. We studied outcomes of cementless total hip arthroplasty using this stem and possible effects of metaphyseal fit on outcomes. Methods. The cementless total hip arthroplasty using this stem was performed for 155 hips. One hundred and thirty-seven hips of 122 patients were followed for 5 to 16 (mean, 9.7) years and entered into the study. The metaphyseal fit was defined as good or poor in an anteroposterior radiograph after surgery. We studied the fixation of the stem and bone reaction on an anteroposterior radiograph at the final followup. Results. Twelve hips had revision, six acetabular components and six acetabular liners. No stem was revised. The biological fixation of the stem was bone ingrown fixation for 136 hips and unstable for one. The metaphyseal fit was good for 83 hips and poor for 54 hips. There were no differences for stem fixation and bone reaction between the two groups. Conclusions. The fixation of the stem was stable at a mean followup of 9.7 years independently from metaphyseal fit.

BACKGROUND: Dry eye has shown a marked increase due to visual display terminal (VDT) use. It remains unclear whether reduced blinking while focusing can have a direct deleterious impact on the lacrimal gland function. To address this issue that potentially affects the life quality, we conducted a large-scale epidemiological study of VDT users and an animal study. METHODOLOGY/PRINCIPAL FINDINGS: Cross sectional survey carried out in Japan. A total of 1025 office workers who use VDT were enrolled. The association between VDT work duration and changes in tear film status, precorneal tear stability, lipid layer status and tear secretion were analyzed. For the animal model study, the rat VDT user model, placing rats onto a balance swing in combination with exposure to an evaporative environment was used to analyze lacrimal gland function. There was no positive relationship between VDT working duration and change in tear film stability and lipid layer status. The odds ratio for decrease in Schirmer score, index of tear secretion, were significantly increased with VDT working year (P = 0.012) and time (P = 0.005). The rat VDT user model, showed chronic reduction of tear secretion and was accompanied by an impairment of the lacrimal gland function and morphology. This dysfunction was recovered when rats were moved to resting conditions without the swing. CONCLUSIONS/SIGNIFICANCE: These data suggest that lacrimal gland hypofunction is associated with VDT use and may be a critical mechanism for VDT-associated dry eye. We believe this to be the first mechanistic link to the pathogenesis of dry eye in office workers.

Aims. To determine the efficacy of a new distal protection method in SFA CTO interventions. Methods and Results. From June 2003 to February 2009, ninety-two consecutive, chronic total occlusions of superficial femoral arteries were treated with catheter-based intervention using a bidirectional approach. Nine of these cases were managed with our original, distal protection method, based on symptoms, angiographic images, wire resistance, and intravascular ultrasound images. The average age was 73 years; eight patients were male. The mean occlusion length was 17.1 cm. A distal protection balloon was inserted from the retrograde sheath in the popliteal artery and placed distal to the occluded lesion after successful wire crossing. Lesion dilatation with a balloon was performed antegradely and debris was removed by 6Fr. guiding catheter. Debris was retrieved from all lesions, consisting mainly of thrombus. Where we decided not to use the distal protection method, there was no distal thromboembolism. Conclusion. In SFA-CTO intervention, the risk of distal embolization is 10%, which can be anticipated and eliminated by the distal protection method.