Search

Stable organic luminescent radicals have attracted much attention, but their stability under light irradiation is not yet satisfactory. New luminescent radicals (TTMs) based on terminal benzene ring modified carbazole donors were synthesized and evaluated. Their photostability (half-life under continuous laser irradiation) has improved by 1 order of magnitude compared to simple carbazole donors. This is a new molecular design strategy to improve the photostability of luminescent radicals without reducing other photophysical properties.

Introduction In cerebral blood flow (CBF) quantification with pseudo-continuous arterial spin labeling (pCASL) MRI, arterial blood T1 (T1a) is usually fixed to a typical value (e.g., 1650 ms). However, individual T1a depends strongly on hematocrit (Hct) level. To investigate the utility of Hct-based T1a as an alternative to the fixed T1a method, we performed a comparative study with 15O-water positron emission tomography (PET). Methods For patients with unilateral occlusion or stenosis of major arteries, hemispheric CBF on the healthy side was measured using pCASL and 15O-water PET. The pCASL CBFs were calculated with both (a) fixed T1a (1650 ms) and (b) individual T1a estimated from blood-sampled Hct (Hct-based T1a). Correlation coefficients of Hct–CBF were calculated and compared between pCASL and PET. Results In pCASL, CBF with fixed T1a showed a strong negative correlation with Hct (r = −0.568), which was reduced with individual Hct-based T1a (r = −0.341 to −0.190), consistent with the Hct–CBF relation measured with PET (r = −0.349). Discussion and conclusion We demonstrated that Hct-based T1a resulted in smaller inter-individual variations in pCASL CBF and an inverse Hct–CBF relationship more similar to that of PET. Care must be taken in the interpretation of pCASL CBF imaging in relation to Hct level even in subjects without anemia. Further comparative studies are needed to investigate whether advanced techniques improve pCASL CBF quantification at the individual level.

The bidirectional controller of the thermoregulatory center in the preoptic area (POA) is unknown. Using rats, here, we identify prostaglandin EP3 receptor–expressing POA neurons (POA EP3R neurons) as a pivotal bidirectional controller in the central thermoregulatory mechanism. POA EP3R neurons are activated in response to elevated ambient temperature but inhibited by prostaglandin E 2 , a pyrogenic mediator. Chemogenetic stimulation of POA EP3R neurons at room temperature reduces body temperature by enhancing heat dissipation, whereas inhibition of them elicits hyperthermia involving brown fat thermogenesis, mimicking fever. POA EP3R neurons innervate sympathoexcitatory neurons in the dorsomedial hypothalamus (DMH) via tonic (ceaseless) inhibitory signaling. Although many POA EP3R neuronal cell bodies express a glutamatergic messenger RNA marker, their axons in the DMH predominantly release γ-aminobutyric acid (GABA), and their GABAergic terminals are increased by chronic heat exposure. These findings demonstrate that tonic GABAergic inhibitory signaling from POA EP3R neurons is a fundamental determinant of body temperature for thermal homeostasis and fever.

Lymphoepithelial carcinoma (LEC) of the submandibular gland is a very rare neoplasm that constitutes only 0.4 % of the salivary gland neoplasms, mainly involving the parotid glands, and is well known to have a racial prevalence in Southwest Asia, southern China, Africa, and the Arctic Circle. This report describes the case of a 49-year-old Japanese woman who was diagnosed with an LEC of the right submandibular gland. The patient presented with a painless, gradually enlarging mass in the right submandibular gland for 2 years. Computed tomography scanning showed a 20 × 16 mm, slightly enhanced solid mass in the right submandibular gland; magnetic resonance imaging revealed an isointense and hyperintense mass in T1- and T2-weighted images. Fine-needle aspiration cytology revealed a few small salivary gland cells and acidophilic cells against a background of lymphocytes, suggesting Warthin tumor or chronic sialadenitis. The right submandibular gland was resected, and intraoperative frozen section analysis suggested a diagnosis of LEC of the submandibular gland. Histopathological findings from the resected submandibular gland were consistent with a diagnosis of LEC, and a definitive pathologic staging of T3N0M0. Postoperative adjuvant radiation therapy was administered, and the patient was disease free at the 4-year follow-up.

Old animals display significant alterations in sleep-wake patterns such as increases in sleep fragmentation and sleep propensity. Here we demonstrated that dorsomedial hypothalamus-specific PR-domain containing protein 13-knockout (DMH-Prdm13-KO) mice recapitulated age-associated sleep alterations such as sleep fragmentation and increased sleep attempts during sleep deprivation (SD). These phenotypes were further exacerbated during aging, with increased adiposity and decreased physical activity, resulting in shortened lifespan. Dietary restriction (DR), a well-known anti-aging intervention in diverse organisms, ameliorated age-associated sleep alterations, whereas these effects of DR were abrogated in DMH-Prdm13-KO mice. Moreover, overexpression of Prdm13 in the DMH ameliorated sleep fragmentation and excessive sleepiness during SD in old mice. Therefore, maintaining Prdm13 signaling in the DMH might play an important role to control sleep-wake patterns during aging.

Tuberculosis has been attracting attention as a re-emerging infection in recent years. Extrapulmonary tuberculosis in the head and neck region usually takes the form of tuberculous cervical lymphadenitis, and salivary gland tuberculosis is rare. Parotid gland tuberculosis is frequently difficult to differentiate from malignant tumors, and definitive diagnosis is often based on postoperative pathology. We report a case in which we reached a definitive diagnosis by appropriate and careful investigation and immediately initiated antimycobacterial therapy while avoiding surgery. The gentleman in his 70s presented with swelling below the left ear. The only local signs were mild tenderness and swelling, with no reddening of the skin or facial paralysis. Results from fine needle aspiration cytology were suggestive of acid-fast bacterial infection. Following puncture, reddening of the skin and necrosis appeared, and a local biopsy was performed. Pathology demonstrated the presence of Langerhans multinucleated giant cells and epithelioid granuloma. As polymerase chain reaction testing of a sample submitted at the same time was positive for Mycobacterium tuberculosis DNA, parotid gland tuberculosis was diagnosed. Outpatient combination therapy was initiated with isoniazid, ethambutol, and rifampicin, to which the infection was sensitive. Since completion of this oral treatment, the patient has shown an uneventful course, with no parotid gland swelling, cervical lymph node swelling, or signs of recurrence. Parotid gland tuberculosis must always be borne in mind as a differential diagnosis for parotid gland tumors.

Water plays a crucial role in the formation and destruction of biomolecular structures. The mechanism for destroying biomolecular structures was thought to be an active breaking of hydrogen bonds by water molecules. However, using nonequilibrium molecular dynamics simulations, in which an amyloid-β amyloid fibril was destroyed via infrared free-electron laser (IR-FEL) irradiation, we discovered a new mechanism, in which water molecules disrupt protein aggregates. The intermolecular hydrogen bonds formed by C═O and N-H in the fibril are broken at each pulse of laser irradiation. These bonds spontaneously re-form after the irradiation in many cases. However, when a water molecule happens to enter the gap between C═O and N-H, it inhibits the re-formation of the hydrogen bonds. Such sites become defects in the regularly aligned hydrogen bonds, from which all hydrogen bonds in the intermolecular β-sheet are broken as the fraying spreads. This role of water molecules is entirely different from other known mechanisms. This new mechanism can explain the recent experiments showing that the amyloid fibrils are not destroyed by laser irradiation under dry conditions. Additionally, we found that helix structures form more after the amyloid disruption; this is because the resonance frequency is different in a helix structure. Our findings provide a theoretical basis for the application of IR-FEL to the future treatment of amyloidosis.

NA

Spontaneous radiographic disappearance of cerebral aneurysms is often observed under special conditions such as giant aneurysms. However, spontaneous disappearance of an unruptured and nongiant intracranial saccular aneurysms is rare. We describe two cases of this rare vascular phenomenon. The first patient is a 64-year-old female diagnosed with a small unruptured aneurysm arising from the distal anterior cerebral artery. Spontaneous disappearance of the aneurysm on magnetic resonance angiography (MRA) was observed 5 years after the initial diagnosis. Continuous imaging surveillance also revealed spontaneous reappearance of the aneurysm 2 years later. The second patient is a 57-year-old female harboring a small unruptured saccular aneurysm arising from the M1–M2 bifurcation of the middle cerebral artery. The aneurysm showed spontaneous disappearance on MRA 13 years after the initial diagnosis. These cases provide a new insight into this natural dynamic process even in cases of a small unruptured intracranial saccular aneurysm.

CRISPR-Cas9 are widely used for gene targeting in mice and rats. The non-homologous end-joining (NHEJ) repair pathway, which is dominant in zygotes, efficiently induces insertion or deletion (indel) mutations as gene knockouts at targeted sites, whereas gene knock-ins (KIs) via homology-directed repair (HDR) are difficult to generate. In this study, we used a double-stranded DNA (dsDNA) donor template with Cas9 and two single guide RNAs, one designed to cut the targeted genome sequences and the other to cut both the flanked genomic region and one homology arm of the dsDNA plasmid, which resulted in 20–33% KI efficiency among G0 pups. G0 KI mice carried NHEJ-dependent indel mutations at one targeting site that was designed at the intron region, and HDR-dependent precise KIs of the various donor cassettes spanning from 1 to 5 kbp, such as EGFP, mCherry, Cre, and genes of interest, at the other exon site. These findings indicate that this combinatorial method of NHEJ and HDR mediated by the CRISPR-Cas9 system facilitates the efficient and precise KIs of plasmid DNA cassettes in mice and rats. Electronic supplementary material The online version of this article (10.1007/s00439-020-02198-4) contains supplementary material, which is available to authorized users.

BACKGROUND Aplastic or twiglike middle cerebral artery (Ap/T-MCA) is a rare anomaly characterized by a unilateral MCA occlusion with plexiform vessels that causes hemorrhagic and (less commonly) ischemic strokes. The reasons for this are rarely discussed, and thus optimal treatment for ischemic Ap/T-MCA remains controversial. Here, the authors report a case of Ap/T-MCA with transient ischemic attacks treated by bypass surgery and discuss the mechanism of ischemic development and treatment methods. OBSERVATIONS A 62-year-old hypertensive man with transient, recurrent left hemiparesis visited the authors’ hospital. Magnetic resonance angiography showed proximal occlusion of the right MCA and stenosis in the left MCA. Digital subtraction angiography revealed occlusion of the right MCA and abnormal vascular networks, leading to a diagnosis of Ap/T-MCA with contralateral MCA stenosis. Antiplatelet therapy with aspirin was insufficient, and a superficial temporal artery–MCA bypass was performed. There were no ischemic or hemorrhagic events postoperatively. LESSONS Atherosclerosis seems to have a significant impact on the development of ischemic stroke in patients with Ap/T-MCA, and the presence of coexisting atherosclerotic stenotic vascular lesions outside the Ap/T-MCA site is substantial in its development. Bypass surgery is a promising treatment option for ischemic Ap/T-MCA.

BACKGROUND Infected intracranial aneurysms are relatively rare but tend to occur in multiple locations. Establishing an optimal treatment strategy for multiple ruptured aneurysms is often challenging, especially when simultaneous ruptures occur in different locations. We report a case of simultaneous intracerebral and subarachnoid hemorrhages caused by the rupture of multiple infected intracranial aneurysms. OBSERVATIONS A 23-year-old male with a 2-week history of chronic fever presented with sudden onset of severe headache and visual disturbance. Computed tomography showed intracerebral hemorrhage in the right occipital lobe and subarachnoid hemorrhage in the area of the left Sylvian fissure. Further investigation documented Staphylococcus bacteremia, verrucae on the mitral valve, and aneurysms arising from the right posterior cerebral artery (PCA) and the left middle cerebral artery (MCA). A larger aneurysm arising from the PCA was successfully occluded endovascularly, but subsequent endovascular occlusion of the MCA aneurysm was unsuccessful because some important branches were observed extending from the aneurysm. The left MCA aneurysm was then obliterated by angioplastic clipping via left pterional craniotomy. The patient showed a favorable neurological recovery after treatment. LESSONS In such complex cases of infectious aneurysms, the method and timing of treatment need to be carefully determined based on the medical condition.

In addition to maintaining a constant core body temperature, the mammalian thermoregulatory system, including that in humans deviates body temperature from the normally defended range as necessary to protect the organism from various environmental stressors, such as ambient temperature (heat and cold), pathogens, natural enemies, and starvation. Recent studies have reported that neural circuits of the brain are involved in thermoregulatory responses to environmental stresses. This article summarizes the most recent findings on the central neural network associated with thermoregulatory physiological responses to environmental stresses.