A Case of Nivolumab-Induced Severe Mononeuropathy Multiplex and Rhabdomyolysis

We report an 81-year-old man with multiple liver metastases after tumorectomy for primary mediastinal malignant melanoma, who experienced limb weakness and sensory disturbance after nivolumab monotherapy. He was diagnosed with nivolumab-induced mononeuropathy multiplex and rhabdomyolysis based on serologic examination, muscle biopsy, magnetic resonance imaging of the limbs, and a nerve conduction study. A course of intravenous methylprednisolone (mPSL) was initiated at 1 g/day for 3 days. After that, oral prednisolone (PSL) was started at 1 mg/kg/day and gradually tapered. Limb muscle strength improved, but when PSL was reduced to 0.3 mg/kg/day, the weakness recurred, and a nerve conduction study showed exacerbation of mononeuropathy multiplex. The patient was again administered intravenous mPSL (0.5 g/day for 3 days) followed by oral PSL at 0.5 mg/kg/day, and his neurological symptoms improved. Nivolumab, an immune checkpoint inhibitor, is used for the treatment of advanced melanoma and other cancers and causes various immune-related adverse events (irAEs). However, neurological irAEs related to nivolumab are rare. Furthermore, there are no reports of simultaneous nerve and muscle impairment. Unexpected irAEs affecting various organs should be recognized and treated appropriately

Fairness Scheduling in Dense User-Centric Cell-Free Massive MIMO Networks

We consider a user-centric scalable cell-free massive MIMO network with a total of $LM$ distributed remote radio unit antennas serving $K$ user equipments (UEs). Many works in the current literature assume $LM\gg K$, enabling high UE data rates but also leading to a system not operating at its maximum performance in terms of sum throughput. We provide a new perspective on cell-free massive MIMO networks, investigating rate allocation and the UE density regime in which the network makes use of its full capability. The UE density $K$ approximately equal to $\frac{LM}{2}$ is the range in which the system reaches the largest sum throughput. In addition, there is a significant fraction of UEs with relatively low throughput, when serving $K>\frac{LM}{2}$ UEs simultaneously. We propose to reduce the number of active UEs per time slot, such that the system does not operate at ``full load'', and impose throughput fairness among all users via a scheduler designed to maximize a suitably defined concave componentwise non-decreasing network utility function. Our numerical simulations show that we can tune the system such that a desired distribution of the UE throughput, depending on the utility function, is achieved

Overloaded Pilot Assignment with Pilot Decontamination for Cell-Free Systems

The pilot contamination in cell-free massive multiple-input-multiple-output (CF-mMIMO) must be addressed for accommodating a large number of users. In previous works, we have investigated a decontamination method called subspace projection (SP). The SP separates interference from co-pilot users by using the orthogonality of the principal components of the users' channel subspaces. Non-overloaded pilot assignment (PA), where each radio unit (RU) does not assign the same pilot to different users, limits the spectral efficiency (SE) of the system, since SP channel estimation is able to deal with co-pilot users that have nearly orthogonal subspaces. Motivated by this limitation, this paper introduces overloaded PA methods adjusted for the decontamination in order to improve the sum SE of CF systems. Numerical simulations show that the overloaded PA methods give higher SE than that of non-overloaded PA at a high user density scenario.Comment: 7 pages, 2 figures, this paper was submitted to IEEE WCNC 202

FoxO1 Gain of Function in the Pancreas Causes Glucose Intolerance, Polycystic Pancreas, and Islet Hypervascularization

Genetic studies revealed that the ablation of insulin/IGF-1 signaling in the pancreas causes diabetes. FoxO1 is a downstream transcription factor of insulin/IGF-1 signaling. We previously reported that FoxO1 haploinsufficiency restored β cell mass and rescued diabetes in IRS2 knockout mice. However, it is still unclear whether FoxO1 dysregulation in the pancreas could be the cause of diabetes. To test this hypothesis, we generated transgenic mice overexpressing constitutively active FoxO1 specifically in the pancreas (TG). TG mice had impaired glucose tolerance and some of them indeed developed diabetes due to the reduction of β cell mass, which is associated with decreased Pdx1 and MafA in β cells. We also observed increased proliferation of pancreatic duct epithelial cells in TG mice and some mice developed a polycystic pancreas as they aged. Furthermore, TG mice exhibited islet hypervascularities due to increased VEGF-A expression in β cells. We found FoxO1 binds to the VEGF-A promoter and regulates VEGF-A transcription in β cells. We propose that dysregulation of FoxO1 activity in the pancreas could account for the development of diabetes and pancreatic cysts

A new Miocene whale-fall community dominated by the bathymodiolin mussel Adipicola from the Hobetsu area, Hokkaido, Japan

金沢大学理工研究域地球社会基盤学系We report the fourth record of a fossil whale-fall community in Japan. The new material consists of a single whale bone in association mainly with small bathymodiolin mussels, Adipicola sp., found in the Karumai Formation (late middle Miocene—early late Miocene) in the Hobetsu area of Hokkaido, Japan. This association of whale bone and Adipicola sp. and its mode of occurrence resembles the description of some other ancient whale-fall communities dominated by small mussels from the Olympic Peninsula in Washington State (early Oligocene), Shosanbetsu in Hokkaido (early middle Miocene) and Carpineti in northern Italy (middle Miocene) and constitutes an example of a chemosynthesis-based community sustained by whale-fall decay in the Miocene deep sea. The new example extends the Miocene distribution of bathymodiolin-dominated whale-fall communities to the northwestern Pacific Ocean

Association between the tissue accumulation of advanced glycation end products and exercise capacity in cardiac rehabilitation patients

Background Advanced glycation end products (AGEs) are associated with aging, diabetes mellitus (DM), and other chronic diseases. Recently, the accumulation of AGEs can be evaluated by skin autofluorescence (SAF). However, the relationship between SAF levels and exercise capacity in patients with cardiovascular disease (CVD) remains unclear. This study aimed to investigate the association between the tissue accumulation of AGEs and clinical characteristics, including exercise capacity, in patients with CVD. Methods We enrolled 319 consecutive CVD patients aged >= 40 years who underwent early phase II cardiac rehabilitation (CR) at our university hospital between November 2015 and September 2017. Patient background, clinical data, and the accumulation of AGEs assessed by SAF were recorded at the beginning of CR. Characteristics were compared between two patient groups divided according to the median SAF level (High SAF and Low SAF). Results The High SAF group was significantly older and exhibited a higher prevalence of DM than the Low SAF group. The sex ratio did not differ between the two groups. AGE levels showed significant negative correlations with peak oxygen uptake and ventilator efficiency (both P <0.0001). Exercise capacity was significantly lower in the high SAF group than in the low SAF group, regardless of the presence or absence of DM (P <0.05). A multivariate logistic regression analysis showed that SAF level was an independent factor associated with reduced exercise capacity (odds ratio 2.10; 95% confidence interval 1.13-4.05; P = 0.02). Conclusion High levels of tissue accumulated AGEs, as assessed by SAF, were significantly and independently associated with reduced exercise capacity. These data suggest that measuring the tissue accumulation of AGEs may be useful in patients who have undergone CR, irrespective of whether they have DM

Spindle microtubules generate tension-dependent changes in the distribution of inner kinetochore proteins

The N and C termini of CENP-T undergo tension-dependent separation, suggesting that CENP-T elongation is responsible for changes in the shape of the inner kinetochore

看護学部における地域住民参画型教育の取り組みと今後の課題 : 模擬患者の養成と看護OSCEへの参画支援を通して

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Decline in subarachnoid haemorrhage volumes associated with the first wave of the COVID-19 pandemic

BACKGROUND: During the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study\u27s objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines. METHODS: We conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March-31 May 2020. The prior 1-year control period (1 March-31 May 2019) was obtained to account for seasonal variation. FINDINGS: There was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI -24.3% to -20.7%, p\u3c0.0001). Embolisation of ruptured aneurysms declined with 1170-1035 procedures, respectively, representing an 11.5% (95%CI -13.5% to -9.8%, p=0.002) relative drop. Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations, a 24.9% relative decline (95% CI -28.0% to -22.1%, p\u3c0.0001). A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1% (95% CI 32.3% to 50.6%, p=0.008) despite a decrease in SAH admissions in this tertile. INTERPRETATION: There was a relative decrease in the volume of SAH hospitalisations, aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic. These findings in SAH are consistent with a decrease in other emergencies, such as stroke and myocardial infarction

Diurnal changes in salmon GnRH secretion in the brain of masu salmon (Oncorhynchus masou)

The day night changes of salmon GnRH (sGnRH), which is secreted from various brain regions, were analyzed in maturing and matured masu salmon (Oncorhynchus masou). In maturing males, the levels of sGnRH secreted from the olfactory bulb (OB), terminal nerve (TN), and ventral telencephalon and preoptic area (VT+POA) were all significantly higher during midnight than daytime. However, the contents of sGnRH in the pituitary gland during midnight were not higher than those during daytime. In maturing females, the levels of sGnRH secreted from the VT+POA were higher during midnight than daytime, and the contents of sGnRH in the pituitary gland were also higher during midnight. In matured fish, the levels of sGnRH secreted from the OB, TN and VT+POA during midnight were significantly higher than those during daytime. There were also no significant differences in the contents of sGnRH in the pituitary gland. These results suggest that a short photoperiod may be involved in diurnal secretion rhythms of sGnRH in various brain regions and the pituitary gland. (C) 2013 Elsevier Inc. All rights reserved