Investigating changes in the premotor cortex-derived frontal-striatal-thalamic subcircuit in attenuated psychosis syndrome.

Frontal-striatal-thalamic circuit impairment is presumed to underlie schizophrenia. Individuals with attenuated psychosis syndrome (APS) show longitudinal volume reduction of the putamen in the striatum, which has a neural connection with the premotor cortex through the frontal-striatal-thalamic subcircuit. However, comprehensive investigations into the biological changes in the frontal-striatal-thalamic subcircuit originating from the premotor cortex in APS are lacking. We investigated differences in fractional anisotropy (FA) values between the striatum and premotor cortex (ST-PREM) and between the thalamus and premotor cortex (T-PREM) in individuals with APS and healthy controls, using a novel method TractSeg. Our study comprised 36 individuals with APS and 38 healthy controls. There was a significant difference between the control and APS groups in the right T-PREM (odds ratio = 1.76, p = 0.02). Other factors, such as age, sex, other values of FA, and antipsychotic medication, were not associated with differences between groups. However, while FA value reduction of ST-PREM and T-PREM in schizophrenia has been previously reported, in the present study on APS, the alteration of the FA value was limited to T-PREM in APS. This finding suggests that ST-PREM impairment is not predominant in APS but emerges in schizophrenia. Impairment of the neural network originating from the premotor cortex can lead to catatonia and aberrant mirror neuron networks that are presumed to provoke various psychotic symptoms of schizophrenia. Our findings highlight the potential role of changes in a segment of the frontal-thalamic pathway derived from the premotor cortex as a biological basis of APS.

Exploring the impact of biological alterations in the superior thalamic radiations on exploratory eye movements in attenuated psychosis syndrome.

Introduction: Aberrant fixation and scan paths in visual searches have been repeatedly reported in schizophrenia. The frontal eye fields (FEF) and thalamus may be responsible for fixation and scan paths. These two regions are connected by superior thalamic radiation (STR) in humans. Studies have reported reduced fixation numbers and shortened scan path lengths in individuals with attenuated psychosis syndrome (APS) and schizophrenia. In this study, we hypothesized that STRs in the white matter fiber bundles of impairments underlie abnormalities in fixation and scan path length in individuals with APS. Methods: Twenty-one individuals with APS and 30 healthy controls participated in this study. All participants underwent diffusion tensor imaging, and fractional anisotropy (FA) values of the left and right STR were analyzed using the novel method TractSeg. The number of eye fixations (NEF), total eye scanning length (TESL), and mean eye scanning length (MESL), derived using the exploratory eye movement (EEM) test, were adopted to evaluate the fixation and scan path length. We compared the FA values of the bilateral STR and EEM parameters between the APS and healthy control groups. We investigated the correlation between bilateral STR and EEM parameters in the APS and healthy control groups. Results: NEF, TESL, MESL, and the FA values of the left STR were significantly reduced in individuals with APS compared to healthy controls. The left STR FA value in the APS group was significantly positively correlated with the MESL (r = 0.567, p = 0.007). In addition, the right STR FA value of the APS group was significantly correlated with the TESL (r = 0.587, p = 0.005) and MESL (r = 0.756, p = 0.7×10-4). Discussion: These results demonstrate that biological changes in the STR, which connects the thalamus and FEF, underlie abnormalities in fixation and scanning. Recently, aberrations in the thalamus-frontal connection have been shown to underlie the emergence of psychotic symptoms. STR impairment may be a part of the biological basis of APS in individuals with subthreshold psychotic symptoms.

Nomenclature for psychosis risk in Japan: Survey results from high-risk individuals, caregivers, and mental health professionals.

BACKGROUND: Labeling terms for high-risk state for psychosis, such as 'ultra-high risk' (UHR), 'attenuated psychosis syndrome' (APS), and 'at-risk mental state' (ARMS), have been criticized for their potential to lead to stigma. Hence, mental health service users in Melbourne recently proposed new terms illustrating the at-risk concept ['pre-diagnosis stage' (PDS), 'potential of developing a mental illness' (PDMI), and 'disposition for developing a mental illness' (DDMI)]. We aimed at testing the suitability of these existing and new terms in the clinical settings of early psychiatric intervention in Japan. METHODS: At two centers of early intervention (Toyama and Tokyo), a questionnaire on the understanding and opinion of high-risk terminology was administered to 62 high-risk patients, 44 caregivers, and 64 clinicians. The questionnaire contained the existing and new terms, where the term ARMS was translated into two different Japanese terms ARMS-psychosis and ARMS-kokoro. Participants' opinion on the disclosure of high-risk status was also obtained. RESULTS: ARMS-kokoro was most preferred, least stigmatizing, and best explaining the patients' difficulties for all groups, while UHR and other terms including the Japanese word 'psychosis' (i.e., APS and ARMS-psychosis) were not preferred. New labeling terms were generally not well received. All groups preferred full disclosure of high-risk terms by the psychiatrist with or without the presence of family members. CONCLUSION: The term ARMS-kokoro was commonly accepted as a favorable labeling term for the high-risk state for psychosis in Japan. However, another translation ARMS-psychosis was considered stigmatizing, demonstrating the importance of appropriate translation of high-risk terminology into local languages.

Associations between Verbal Fluency and Asymmetry of White Matter Integrity in the Superior Longitudinal Fasciculus in At-Risk Mental States for Psychosis.

Verbal fluency is one of the most severely impaired components of cognitive function in schizophrenia and is also impaired in at-risk mental states (ARMSs) for psychosis. The aim of this study was to explore the markers of disease progression in subjects with ARMSs by comparing the association between the white matter integrity of the superior longitudinal fasciculus (SLF) and verbal fluency in subjects with ARMSs and healthy control (HC) subjects. The correlations of the fractional anisotropy (FA) values on diffusion tensor imaging (DTI) and the laterality index (LI) values of SLF branches I, II, and III with the verbal fluency performance were analyzed in right-handed subjects with ARMSs (ARMS group; n = 18) and HC subjects (HC group; n = 34) aged 18 to 40 years old. In the HC group compared with the ARMS group, the LI values suggested right lateralization of the SLF II and III. Letter fluency was significantly correlated with the LI of the SLF III in both the ARMS and HC groups. The regression coefficient (ß) of this correlation was calculated using the least squares method and yielded a positive number (73.857) in the ARMS group and a negative number (-125.304) in the HC group. The association of the rightward asymmetry of the SLF III with the verbal fluency performance observed in the HC group appeared to be lost in the ARMS group, and this could serve as one of the markers of the pathological progression to psychosis in patients with schizophrenia.

Supraglottic myxoedema successfully treated orally.

Summary: Myxoedema coma is a severe form of hypothyroidism with multiple organ dysfunction, characterised by an altered state of consciousness and hypothermia. Intravenous thyroid hormone replacement therapy is the preferred treatment for myxoedema. The mortality rate associated with this disease is high, and early detection and intervention are essential. Supraglottal myxoedema is a rare form of periglottic oedema and can be fatal. A previously healthy 66-year-old man presented with impaired consciousness, hypothermia, and nonpitting oedema. Blood tests revealed the presence of hypothyroidism and respiratory acidosis. He was intubated for type 2 respiratory failure; however, severe laryngeal oedema made the procedure difficult to perform. Oral thyroid hormone therapy was initiated under the diagnosis of myxoedema coma. Tracheostomy was performed because of prolonged type 2 respiratory failure and laryngeal oedema. Three weeks after admission, the patient was weaned off the ventilator. Approximately a week later, laryngeal oedema improved, and the tracheostomy tube was removed. The patient was discharged and remained stable for 3 months. This case report describes a patient with comatose myxoedema and supraglottic oedema who was successfully treated with oral medication alone. This case shows that supraglottic oedema should be considered even in the absence of wheezing or other signs of upper airway obstruction. Learning points: Myxoedema coma is a differential diagnosis of respiratory acidosis. In myxoedematous coma, the possibility of difficult intubation due to supraglottic oedema should be considered. Tracheostomy should be considered for supraglottic myxoedema, which often results in prolonged ventilator use. Supraglottic myxoedema can be treated with oral medications.

Experimental investigation of the effective point of measurement for plane-parallel chambers used in electron beam dosimetry.

In this study, the effective point of measurement (EPOM) for plane-parallel ionization chambers in clinical high-energy electron beams was determined experimentally. Previous studies have reported that the EPOM of plane-parallel chambers is shifted several tens of millimeters downstream from the inner surface of the entrance window to the cavity. These findings were based on the Monte Carlo (MC) simulation, and few experimental studies have been performed. Thus, additional experimental validations of the reported EPOMs were required. In this study, we investigated the EPOMs of three plane-parallel chambers (NACP-02, Roos and Advanced Markus) for clinical electron beams. The EPOMs were determined by comparing the measured percentage depth-dose (PDD) of the plane-parallel chambers and the PDD obtained using the microDiamond detector. The optimal shift to the EPOM was energy-dependent. The determined EPOM showed no chamber-to-chamber variation, thereby allowing the use of a single value. The mean optimal shifts were 0.104 ± 0.011, 0.040 ± 0.012, and 0.012 ± 0.009 cm for NACP-02, Roos, and Advanced Markus, respectively. These values are valid in the R50 range from 2.40 to 8.82 cm, which correspond to 6-22 MeV. Roos and Advanced Markus exhibited similar results to those of the previous studies, but NACP-02 showed a larger shift. This is probably due to the uncertainty of the entrance window of NACP-02. Therefore, it is necessary to carefully consider where the optimal EPOM is located when using this chamber.

[A case of rectovaginal metastasis 6 years after initial resection of extra-gastrointestinal stromal tumor of vulvar origin].

A 53-year-old woman who had undergone excision of KIT-positive extra-gastrointestinal stromal tumor (EGIST) of the vulva 6 years ago presented to our hospital due to a positive fecal occult blood test. Colonoscopy revealed a submucosal tumor in the rectum ventral side. In addition, computed tomography and magnetic resonance imaging revealed a tumor in the rectovaginal septum. For diagnostic and therapeutic purposes, the tumor was resected via the perineal approach. The resected specimen analysis revealed a KIT-positive gastrointestinal stromal tumor (GIST). Following immunopathological and genetic mutation identifications, GIST of the rectovaginal septum from vulva EGIST metastasis was diagnosed. It is important to consider primary GIST and metastatic GIST as differential diagnoses in the case of a rectal submucosal tumor detected by endoscopy.

[A case of upper gastrointestinal bleeding due to a ruptured gastric aneurysm caused by arteriosclerosis derived from primary aldosteronism-induced hypertension].

A 77-year-old woman with a history of hypertension underwent upper gastrointestinal endoscopy for hematemesis, and vasodilation with erosion was detected. Contrast-enhanced computed tomography and abdominal angiography revealed a gastric aneurysm penetrating the stomach wall. Endoscopic hemostasis was thought to be not applicable to a ruptured aneurysm. Transcatheter arterial embolization was not performed because of technical difficulties. Therefore, local gastric resection was performed. It was later determined that the cause of the persistent hypertension was primary aldosteronism, which was thought to cause arteriosclerotic obstruction of the celiac, common hepatic, and splenic arteries, resulting in the formation of the gastric arterial aneurysm. In the case of upper gastrointestinal bleeding, keeping primary aldosteronism in mind as a differential diagnosis is important to make a precise diagnosis and suitable treatment selection.

Controlled cell adhesion using a biocompatible anchor for membrane-conjugated bovine serum albumin/bovine serum albumin mixed layer.

We report here a method for controlling cell adhesion, allowing simple yet accurate cell detachment from the substrate, which is required for the establishment of new cytometry-based cell processing and analyzing methods. A biocompatible anchor for membrane (BAM) was conjugated with bovine serum albumin (BSA) to produce a cell-anchoring agent (BAM-BSA). By coating polystyrene substrates with a mixture of BAM-BSA and BSA, controlled suppression of the substrate's adhesive properties was achieved. Hook-shaped nanoneedles were used to pick up cells from the substrate, while recording the cell-substrate adhesion force, using an atomic force microscope (AFM). Due to the lipid bilayer targeting property of BAM, the coated surface showed constant adhesion forces for various cell lines, and controlling the BAM-BSA/BSA ratio enabled tuning of the adhesion force, ranging from several tens of nano-Newtons down to several nano-Newtons. Optimized tuning of the adhesion force also enabled the detachment of cells from BAM-BSA/BSA-coated dishes, using a shear flow. Moreover, the method was shown to be noncell type specific and similar results were observed using four different cell types, including nonadherent cells. The attenuation of cell adhesion was also used to enable the collection of single cells by capillary aspiration. Thus, this versatile and relatively simple method can be used to control the adhesion of various cell types to substrates.

The structure-activity relationship between oxycoumarin derivatives showing inhibitory effects on iNOS in mouse macrophage RAW264.7 cells.

We have investigated the structure-activity relationship between 63 natural oxycoumarin derivatives and their effects on the expression of inducible-nitric oxide synthase (iNOS) induced by lipopolysaccharide. The protein expression of iNOS was screened by Western blot analysis, and four 5,7-dimethoxycoumarins were selected as potent inhibitors of iNOS expression. In terms of structural specificity, the methoxyl group on C-5 and C-7 and the short alkyl chain (1-5 carbons) on C-6 may be essential for the potent activities. These compounds also showed inhibitory effects on nitric oxide generation and mRNA expression of inflammatory mediators, namely, iNOS and COX-2. Interestingly, the inhibitory effect on mRNA expression was specific for iNOS and was not detected for neuronal NOS. It is expected that these compounds will show anti-inflammatory activities via inhibition of the expressions of iNOS and COX-2.

Inhibitory effect of oxycoumarins isolated from the Thai medicinal plant Clausena guillauminii on the inflammation mediators, iNOS, TNF-alpha, and COX-2 expression in mouse macrophage RAW 264.7.

In the present study, we investigated the inhibitory effect of the known oxycoumarins poncitrin (3), osthol (4), and xanthoxyletin (5), newly isolated from Clausena guillauminii (Rutaceae), together with the known carbazoles heptaphylline (1) and 7-methoxyheptaphylline (2) on inducible-nitric oxide synthase (iNOS) expression induced by lipopolysaccharide (LPS) and the NO generation in RAW 264.7 mouse macrophages. Isolation of active oxycoumarins was guided by Western blot analysis of iNOS protein expression. These oxycoumarins showed an inhibitory effect on iNOS protein expression at 10 microM. Further examination of the inhibitory effects of these compounds on inflammation mediators revealed that the synthesis of nitric oxide (NO) and the protein expression of tumor necrosis factor-alpha (TNF-alpha) and cyclooxygenase-2 (COX-2) were inhibited by 5. It was expected that these compounds show anti-inflammatory activities.