Determination of Waste Management Workers' Physical and Psychological Load: A Cross-Sectional Study Using Biometric Data.

Waste management workers experience high stress and physical strain in their work environment, but very little empirical evidence supports effective health management practices for waste management workers. Hence, this study investigated the effects of worker characteristics and biometric indices on workers' physical and psychological loads during waste-handling operations. A biometric measurement system was installed in an industrial waste management facility in Japan to understand the actual working conditions of 29 workers in the facility. It comprised sensing wear for data collection and biometric sensors to measure heart rate (HR) and physical activity (PA) based on electrocardiogram signals. Multiple regression analysis was performed to evaluate significant relationships between the parameters. Although stress level is indicated by the ratio of low frequency (LF) to high frequency (HF) or high LF power in HR, the results showed that compared with workers who did not handle waste, those who did had lower PA and body surface temperature, higher stress, and lower HR variability parameters associated with higher psychological load. There were no significant differences in HR, heart rate interval (RRI), and workload. The psychological load of workers dealing directly with waste was high, regardless of their PA, whereas others had a low psychological load even with high PA. These findings suggest the need to promote sustainable work relationships and a quantitative understanding of harsh working conditions to improve work quality and reduce health hazards.

Fibroblasts as a source of self-antigens for central immune tolerance.

Fibroblasts are one of the most common but also neglected types of stromal cells, the heterogeneity of which underlies the specific function of tissue microenvironments in development and regeneration. In the thymus, autoreactive T cells are thought to be negatively selected by reference to the self-antigens expressed in medullary epithelial cells, but the contribution of other stromal cells to tolerance induction has been poorly examined. In the present study, we report a PDGFR+ gp38+ DPP4- thymic fibroblast subset that is required for T cell tolerance induction. The deletion of the lymphotoxin ß-receptor in thymic fibroblasts caused an autoimmune phenotype with decreased expression of tissue-restricted and fibroblast-specific antigens, offering insight into the long-sought target of lymphotoxin signaling in the context of the regulation of autoimmunity. Thus, thymic medullary fibroblasts play an essential role in the establishment of central tolerance by producing a diverse array of self-antigens.

[A Case of Rapidly Progressing High-grade B-cell Lymphoma with c-Myc Translocation and Bcl-2 Protein Expression].

We report a case of rapidly progressing primary high-grade B-cell lymphoma of the central nervous system with c-Myc translocation and Bcl-2 protein expression that resulted in the patient's death 45 days after the onset of convulsions. Further, we provide a literature review. CASE:A 74-year-old man was admitted to our hospital for convulsions. Magnetic resonance imaging on admission showed tumorous lesions at the left temporoparietal junction. An open biopsy was performed promptly. The patient was diagnosed with primary high-grade B-cell lymphoma of the central nervous system with c-Myc translocation and Bcl-2 protein expression(<50%). The tumor showed rapid progression postoperatively. The patient did not respond to steroids and died 45 days after the onset of convulsions. CONCLUSION:The c-Myc translocation, showing a strong c-Myc protein positivity, and co-expression of the Bcl-2 protein were poor prognostic factors for the tumor.

Soluble RANKL is physiologically dispensable but accelerates tumour metastasis to bone.

Receptor activator of NF-κB ligand (RANKL) is a multifunctional cytokine known to affect immune and skeletal systems, as well as oncogenesis and metastasis1-4. RANKL is synthesized as a membrane-bound molecule, and cleaved into its soluble form by proteases5-7. As the soluble form of RANKL does not contribute greatly to bone remodelling or ovariectomy-induced bone loss8, whether soluble RANKL has a role in pathological settings remains unclear. Here we show that soluble RANKL promotes the formation of tumour metastases in bone. Mice that selectively lack soluble RANKL (Tnfsf11ΔS/ΔS)5-7,9 have normal bone homoeostasis and develop a normal immune system but display markedly reduced numbers of bone metastases after intracardiac injection of RANK-expressing melanoma and breast cancer cells. Deletion of soluble RANKL does not affect osteoclast numbers in metastatic lesions or tumour metastasis to non-skeletal tissues. Therefore, soluble RANKL is dispensable for physiological regulation of bone and immune systems, but has a distinct and pivotal role in the promotion of bone metastases.

[A Case of Successful Drug Management with Dabigatran and Idarucizumab to Address Embolic and Hemorrhagic Complications for Asymptomatic and Traumatic Subdural Hematoma with Non-valvular Atrial Fibrillation].

A 93-year-old woman incurred a head bruise 5 days prior to presentation, and head CT revealed right subacute subdural hematoma. As she was on direct oral anti-coagulant(DOAC)treatment for non-valvular atrial fibrillation(NVAF), the DOAC administration was stopped temporarily to prevent an increase in the size of the hematoma. Dabigatran treatment was initiated after the confirmation of no change in hematoma size and the follow-up CT revealed a reduction in the hematoma. However, left upper limb paresis occurred on day 12 of dabigatran treatment and head CT revealed the onset of right chronic subdural hematoma. Emergency burr hole surgery was performed after intravenous administration of idarucizumab to neutralize the dabigatran. Her neurologic symptoms improved after the operation and no recurrence of subdural hematoma was observed even after dabigatran treatment was resumed. Dabigatran could be administered relatively safely, even for subacute intracranial hemorrhage complicated with NVAF, suggesting the possibility of the prevention of ischemic stroke. Moreover, even when intracranial hemorrhage recurred, the prompt neutralizing effect of idarucizumab, a dabigatran-specific neutralizing agent, was useful in the surgical intervention and perioperative management.

[The Efficacy of Percutaneous Transluminal Angioplasty and Stenting for Traumatic Vertebral Artery Dissection due to Cervical Vertebral Fracture].

A 73-year-old man was admitted at another hospital after a traffic accident. The diagnosis was cervical vertebral fracture. Despite conservative treatment, 5 days later he manifested dysarthria due to cerebellar infarction and was transferred to our hospital. Imaging studies revealed right vertebral arterial dissection at the level of the axial fracture. We performed percutaneous transluminal angioplasty with stenting to address his subacute vertebral artery dissection prior to treating the cervical vertebral fracture using external fixation. His clinical course was good;ischemia did not recur after stenting and his dysarthria disappeared upon rehabilitation. Cerebral angiograms obtained 6 months later revealed no significant in-stent restenosis. While medical management tends to be the first-line treatment of traumatic vertebral artery dissection, percutaneous transluminal angioplasty with stenting is necessary before treating other traumatic lesions to prevent neurologic events.

Usefulness of Consciousness Sedation with Dexmedetomidine and Pentazocine during Endovascular Treatment for Acute Stroke.

We investigated the safety and efficacy of consciousness sedation with dexmedetomidine (DEX) during the endovascular treatment of patients with acute cerebral infarction. Between April 2014 and November 2016, 38 stroke patients underwent endovascular thrombectomy (EVT) under local anesthesia and DEX consciousness sedation. The continuous intravenous administration of low-dose DEX (0.3-0.4 µg/kg/h) was started before entering the operating room. Patients not completely immobilized received an iv bolus of pentazocine (PTZ) and/or DEX (0.5-0.6 µg/kg/h). EVT was performed using a stent retriever and/or direct thrombo-aspiration. DEX sedation was stopped as soon as the operation was finished. A stent retriever was used in 8 (21.1%), direct thrombo-aspiration in 10 (26.3%), a stent retriever plus thrombo-aspiration in 14 (36.8%), and other devices in 6 patients (15.8%). Reperfusion exceeding 50% (thrombolysis in cerebral infarction >2b) was obtained in 30 patients (78.9%). DEX sedation alone immobilized 24 patients (63.2%), 14 (36.8%) required the additional injection of DEX or PTZ when EVT devices were navigated to the lesion. The administration of DEX and PTZ elicited no significant respiratory depression or cardiac dysfunction interfering with the procedures. Consciousness sedation by DEX was effective during the endovascular treatment of acute stroke patients. Under DEX sedation and the injection of PTZ, EVT was possible without significantly changing the patients' vital signs.

Identification of subepithelial mesenchymal cells that induce IgA and diversify gut microbiota.

Immunoglobulin A (IgA) maintains a symbiotic equilibrium with intestinal microbes. IgA induction in the gut-associated lymphoid tissues (GALTs) is dependent on microbial sampling and cellular interaction in the subepithelial dome (SED). However it is unclear how IgA induction is predominantly initiated in the SED. Here we show that previously unrecognized mesenchymal cells in the SED of GALTs regulate bacteria-specific IgA production and diversify the gut microbiota. Mesenchymal cells expressing the cytokine RANKL directly interact with the gut epithelium to control CCL20 expression and microfold (M) cell differentiation. The deletion of mesenchymal RANKL impairs M cell-dependent antigen sampling and B cell-dendritic cell interaction in the SED, which results in a reduction in IgA production and a decrease in microbial diversity. Thus, the subepithelial mesenchymal cells that serve as M cell inducers have a fundamental role in the maintenance of intestinal immune homeostasis.

Nε-(carboxymethyl)lysine Concentration in Debris from Carotid Artery Stenting Correlates Independently with Signal Intensity on T1-Weighted Black-Blood Magnetic Resonance Images.

BACKGROUND AND PURPOSE: Because magnetic resonance imaging (MRI) focuses on the morphological characteristics of carotid artery plaques, its diagnostic value with respect to plaque vulnerability is limited. We examined the correlation between Nε-(carboxymethyl)lysine (CML), a main chemical structure of advanced glycation end-products, and the vulnerability of plaques visualized on MRI scans. MATERIALS AND METHODS: We enrolled 43 patients who had undergone carotid artery stenting (CAS) for carotid artery stenosis; all underwent MRI studies, including black-blood MRI and diffusion-weighted imaging (DWI). The signal intensity ratio (SIR) of plaques to adjacent sternocleidomastoid muscle (P/M) on T1- and T2-weighted images (T1WI, T2WI) was calculated. Protein samples were extracted from debris trapped by a filter device. The concentrations of CML and myeloperoxidase (MPO) were measured by solid-phase enzyme-linked immunosorbent assay. RESULTS: The patients were classified into 2 groups based on their SIR-P/M on T1WI and T2WI scans. We observed a higher incidence of post-CAS DWI lesions in patients with a higher than a lower SIR-P/M on T1WI; the CML and MPO concentrations in their CAS debris were also higher. No such differences were seen in patients with a higher or lower SIR-P/M on T2WI scans. The concentration of CML in CAS debris correlated independently with the SIR-P/M on T1WI of the carotid plaques, and was related to the concentration of MPO in CAS debris. CONCLUSIONS: Our findings suggest CML as a candidate molecular imaging probe for the identification of vulnerable plaques.

Relationship between the Carotid Plaque T1 Relaxation Time and the Plaque-to-Muscle Signal Intensity Ratio on Black-Blood Magnetic Resonance Imaging Scans.

BACKGROUND: Black-blood magnetic resonance imaging (BB-MRI) is useful for the characterization and assessment of carotid artery plaques. The plaque-to-muscle signal intensity (SI) ratio (plaque/muscle ratio [PMR]) is used widely to evaluate plaques. However, the correlation between the PMR and the T1 relaxation time needs to be determined. We measured the T1 relaxation time of carotid plaques using T1 mapping and compared the results with the PMR on BB-MRI scans. METHODS: Between April 2014 and July 2015, 20 patients with carotid artery stenosis were treated by carotid artery stenting. All patients underwent preoperative magnetic resonance plaque imaging. The ratio of the plaque SI to the sternocleidomastoid muscle was calculated on T1-weighted BB-MRI scans. T1 mapping was performed in the region where the vessel was narrowest using the inversion recovery technique. The T1 relaxation time was recorded to determine whether there was a correlation with the PMR. RESULTS: The plaque T1 value was 577.3 ± 143.2 milliseconds; the PMR value obtained on BB-MRI scans was 1.23 ± .27. There was a statistically significant decrease in the T1 value as the PMR increased (P < .0001). CONCLUSIONS: As the T1 relaxation time was well correlated with the PMR on BB-MRI scans, the evaluation of vulnerable plaques using the PMR was reliable and convenient.

Comparison of Flow Impairment during Carotid Artery Stenting Using Two Types of Eccentric Filter Embolic Protection Devices.

We investigated the angiographic findings and the clinical outcomes after carotid artery stenting (CAS) using two different, eccentric filter embolic protection devices (EPDs). Between July 2010 and August 2015, 175 CAS procedures were performed using a self-expandable closed-cell stent and a simple eccentric filter EPD (FilterWire EZ in 86 and Spider FX in 89 procedures). The angiographic findings (i.e., flow impairment and vasospasm) at the level of EPDs, neurologic events, and post-operative imaging results were compared between the FilterWire EZ and the Spider FX groups. The CAS was angiographically successful in all 175 procedures. However, the angiographs were obtained immediately after CAS-detected flow impairment in the distal internal carotid artery (ICA) in 11 (6.3%) and ICA spasms at the level of the EPD in 40 cases (22.9%). The incidence of these complications was higher with FilterWire EZ than Spider FX (ICA flow impairment of 10.5% vs. 2.2%, P = 0.03; vasospasm 30.2% vs. 15.7%, P = 0.03). There were nine neurologic events (5.1%); five patients were presented with transient ischemic attacks, three had minor strokes, and one had a major stroke. New MRI lesions were seen in 25 (29.1%) FilterWire-group and in 36 (40.4%) Spider-group patients. The neurologic events and new MRI lesions were not associated with the type of EPD used. Although the ICA flow impairment may result in neurologic events, there was no significant association between the FilterWire EZ and the Spider FX CAS with respect to the incidence of neurologic events by the prompt treatment such as catheter aspiration.

Relationship between Angiographic Results and Morphology in Sidewall Intracranial Aneurysms after Stent-Assisted Coil Embolization.

BACKGROUND: Stent-assisted coil embolization (SACE) is used to address wide-necked or complex aneurysms. However, as they may recanalize after SACE, predictors of recanalization are needed. We investigated the relationship between follow-up angiographic results and the morphology of sidewall (SW) aneurysms in patients treated by SACE. METHODS: Between September 2010 and September 2014, we performed 80 SACE procedures for SW intracranial aneurysms. Angiographic findings, obtained immediately after the procedure, 3-6 months thereafter, and when aneurysmal recanalization was suspected on MR angiogram scan, were recorded. Morphologically, the SW aneurysms were classified as "outside" (OS) and "partially inside" (PI) based on the curve of the axes of the proximal or distal parent artery with respect to the aneurysmal neck. Follow-up angiographic studies on OS- and PI SW aneurysms were compared. RESULTS: On the initial angiograms, we classified 42 aneurysms as OS and 38 as PI. Immediately after SACE, there was no significant difference in the angiographic findings on OS and PI aneurysms. However, on follow-up angiograms, there was a significant difference in the rate of spontaneous improvement (4 of 42 [OS] versus 21 of 38 [PI], P = .001). We performed additional coil embolization to treat 3 recanalized OS aneurysms. CONCLUSIONS: SW aneurysms classified morphologically as PI tended to occlude progressively even after incomplete occlusion by SACE. In contrast, aneurysms classified as OS must be observed carefully after SACE.

The Safety and Efficacy of Triple Antiplatelet Therapy after Intracranial Stent-Assisted Coil Embolization.

BACKGROUND: Stent-assisted coil embolization is effective for intracranial aneurysms, especially for wide-necked aneurysms; however, the optimal antiplatelet regimens for postoperative ischemic events have not yet been established. We aimed at determining the efficacy and safety of a triple antiplatelet therapy regimen after intracranial stent-assisted coil embolization. METHODS: We retrospectively evaluated patients who underwent stent-assisted coil embolization for unruptured intracranial aneurysms or during the chronic phase of a ruptured intracranial aneurysm (≥ 4 weeks after subarachnoid hemorrhage onset). We recorded the incidence of ischemic and bleeding events 140 days postoperatively. RESULTS: We assessed 79 cases in patients who received either dual (n = 51) or triple (n = 28) antiplatelet therapy. The duration of triple antiplatelet therapy was 49 ± 29 days. Seven patients in the dual group experienced postoperative ischemic events. Compared to the dual group, the triple group had a similar incidence of postoperative bleeding events but a significantly lower incidence of postoperative ischemic events (P < .05). CONCLUSIONS: Triple antiplatelet therapy had a significantly lower incidence of postoperative ischemic events and a similar incidence of postoperative bleeding events 140 days postoperatively.

A manual carotid compression technique to overcome difficult filter protection device retrieval during carotid artery stenting.

BACKGROUND: We investigated the incidence of embolic protection device retrieval difficulties at carotid artery stenting (CAS) with a closed-cell stent and demonstrated the usefulness of a manual carotid compression assist technique. METHODS: Between July 2010 and October 2013, we performed 156 CAS procedures using self-expandable closed-cell stents. All procedures were performed with the aid of a filter design embolic protection device. We used FilterWire EZ in 118 procedures and SpiderFX in 38 procedures. The embolic protection device was usually retrieved by the accessory retrieval sheath after CAS. We applied a manual carotid compression technique when it was difficult to navigate the retrieval sheath through the deployed stent. We compared clinical outcomes in patients where simple retrieval was possible with patients where the manual carotid compression assisted technique was used for retrieval. RESULTS: Among the 156 CAS procedures, we encountered 12 (7.7%) where embolic protection device retrieval was hampered at the proximal stent terminus. Our manual carotid compression technique overcame this difficulty without eliciting neurologic events, artery dissection, or stent deformity. CONCLUSIONS: In patients undergoing closed-cell stent placement, embolic protection device retrieval difficulties may be encountered at the proximal stent terminus. Manual carotid compression assisted retrieval is an easy, readily available solution to overcome these difficulties.

Nε-(carboxymethyl)lysine in debris from carotid artery stenting: multiple versus nonmultiple postoperative lesions.

BACKGROUND: No predictor of postoperative ischemic events has been identified in patients undergoing carotid artery stenting (CAS). We aimed to determine whether N(ε)-(carboxymethyl)lysine (CML) in debris trapped by an embolic protection filter device is a predictor of postoperative ischemic events. METHODS: We enrolled 27 patients (73.4 ± 7.2 years; 22 male, 5 female) who underwent CAS for carotid artery stenosis. Diffusion-weighted magnetic resonance imaging was performed before and after the procedure. Protein samples were extracted from the debris. CML and myeloperoxidase were examined by solid phase enzyme-linked immunosorbent assay and Western blot analysis. RESULTS: Seventeen patients had 0 or 1 new lesion (nonmultiple lesions) postoperatively, whereas 10 patients had 2 or more new lesions postoperatively (multiple lesions). The CML concentration of the protein sample was significantly higher in patients with multiple lesions than in those with nonmultiple lesions (6.26 ± 2.77 ng/mg protein and 3.36 ± 1.57 ng/mg protein, respectively; P = .010). Statin therapy for dyslipidemia was associated with a lower incidence of multiple lesions and a lower concentration of CML in the protein sample (P = .004 and P = .02, respectively). Receiver operating characteristic analysis showed that the area under the curve for CML was significantly greater than .5 (.877; 95% confidence interval, .742-1.00). CONCLUSIONS: CML derived from debris may distinguish between patients with postoperative multiple ischemic lesions and those with postoperative nonmultiple lesions who undergo CAS.

Onset Time of Ischemic Events and Antiplatelet Therapy after Intracranial Stent-assisted Coil Embolization.

BACKGROUND: Stent-assisted coil embolization is effective for intracranial aneurysms, especially wide-necked aneurysms; however, the optimal antiplatelet regimens for ischemic events that develop after coil embolization have not yet been established. We aimed to determine the onset time of such postoperative ischemic events and the relationship between these events and antiplatelet therapy. METHODS: We performed coil embolization using a vascular reconstruction stent for 43 cases of intracranial aneurysms and evaluated the incidence of postoperative ischemic events in these cases. RESULTS: Nine patients showed postoperative ischemic events during the follow-up period (13 ± 7 months). Two patients developed cerebral infarction within 24 hours. Five patients developed transient ischemic attack within 40 days while they were receiving dual antiplatelet therapy. In addition, 1 patient showed cerebral infarction 143 days postoperatively during single antiplatelet therapy, and a case of transient visual disturbance was reported 191 days postoperatively (49 days after antiplatelet therapy had been discontinued). We increased the number of antiplatelet agents in 4 of these patients. The other 5 patients were under strict observation with dual antiplatelet therapy. All these patients were shifted to single antiplatelet therapy 3-13 months postoperatively. No recurrence of ischemic events was noted. CONCLUSIONS: Postoperative ischemic events are most likely to occur within 40 days postoperatively. For patients with postoperative ischemic events, additional ischemic events can be prevented by increasing the number of antiplatelet agents; subsequently, they can be shifted to single antiplatelet therapy after the risk of recurrence has decreased.

Treatment outcomes of carotid artery stenting with two types of distal protection filter device.

PURPOSE: Preventing cerebral embolism from debris produced during carotid artery stenting (CAS) is important. This study compared the treatment outcomes of CAS using two types of filter-based embolic protection devices currently in use in Japan. MATERIALS AND METHODS: We assessed 121 consecutive cases of CAS performed with FilterWire EZ™ between July 2010 and November 2012 and 37 consecutive cases of CAS performed with the Spider FX™ between November 2012 and June 2013. A Carotid Wallstent™ was used in all cases. The incidence of positive lesions on diffusion-weighted magnetic resonance imaging (DWI) and stroke were compared between the groups. RESULTS: Postoperative DWI-positive lesions were observed in 38 (31.4%) and 14 (37.8%) patients in the FilterWire and Spider groups, respectively. In the FilterWire group, complications were transient ischemic attacks in 3 (2.5%) patients, cerebral infarction in 2 (1.7%) patients (1 patient each with minor and major stroke), and cerebral hemorrhage due to hyperperfusion syndrome in 1 (0.8%) patient. In the Spider group, except for cerebral infarction (minor stroke) in 1 (2.7%) patient, no complications were observed. No significant differences were observed in the incidence of complications between the groups. CONCLUSION: FilterWire EZ and Spider FX are comparable in terms of treatment outcome.

Intracranial tuberculoma in non-immunosuppressive state.

The rise in the incidence of tuberculosis is generally related to human immunodeficiency virus infection. However, intracranial tuberculoma, a complication of tuberculosis considered to be a critical disease, can develop even in the absence of immunosuppressive state. Here, we describe 2 cases of intracranial tuberculoma occurring in patients with no evidence of immunosuppressive state or past history of tuberculosis. In Case 1, lesions were observed in the right lateral ventricle, with histological examination revealing granulomatous lesions. In Case 2, scattered lesions were observed in the cranium and the lung fields. In both cases, the QuantiFERON Test (QFT) was positive, and improvements were observed in the symptoms following administration of antituberculous drugs. Intracranial tuberculoma cannot be considered rare, and needs to be included in the differential diagnosis of intracranial lesions. Diagnosis can be tricky since this disease can develop in a patient in a non-immunosuppressive state or without a past history of tuberculosis. The QFT is an effective test to enable the diagnosis of tuberculomas in atypical patients.

Cilostazol reduces periprocedural hemodynamic depression in carotid artery stenting.

The clinical effects of two different types of antiplatelet drugs, cilostazol and thienopyridine drugs, were compared in patients treated by carotid artery stenting (CAS). Two hundred patients scheduled for CAS were randomized to either cilostazol or a thienopyridine drug (ticlopidine or clopidogrel). The study was conducted in open-label design. Aspirin was also given to all patients. All episodes of periprocedural hemodynamic instability (bradycardia, hypotension) were recorded together with all instances of stroke, cardiac morbidity, and death within 30 days of the procedure. Angiographic follow-up studies were conducted about 6 months after CAS. Finally, 197 patients were enrolled in this study; 97 were treated with cilostazol (cilostazol group) and 100 with a thienopyridine drug (thienopyridine group). In the 30-day follow-up period, the incidence of stroke, cardiac adverse effects, and death was not significantly different between the 2 groups (cilostazol group 7.2%, thienopyridine group 11.0%; p = 0.85). The incidence of intra- and postprocedural bradycardia was significantly lower in the cilostazol group (cilostazol group 18.6% and 2.1%, thienopyridine group 40.0% and 18.0%, respectively; p < 0.01). Although the incidence of intraprocedural hypotension did not significantly differ between the 2 groups, postprocedural hypotension was significantly lower in the cilostazol group (16.5% vs. 34.0%, p < 0.01). In-stent restenosis on follow-up angiograms was lower in the cilostazol group but not significantly (0% vs. 4.4%, p = 0.12). This small open-label study shows that cilostazol may reduce periprocedural bradycardia and hypotension compared with thienopyridine drugs in patients treated by CAS.