The Long-Term Natural History of Fibrous Dysplasia.

Fibrous dysplasia (FD), a developmental, nonfamilial, benign anomaly of bone development, is characterized by the replacement of normal bone by proliferating fibro-osseous tissue. Marked craniofacial deformities, functional disturbances, and emotional stress are major indications for treatment, and various surgical procedures have been performed; however, excision and regrowth issues have also been reported. While several treatment options are available, no studies have reported the natural history of untreated FD. Here, we report 2 patients, aged 73 and 50 years, respectively, who had not received treatment. Both patients presented to the hospital complaining of noise when moving their heads. Computed tomography scans showed niveau with honeycomb cavities in both patients, indicating abscess formation, and resection was performed. Relatively large cranial FD leads to the development of central necrosis over time. In such cases, surgical intervention should be performed at an early disease stage.

Alveolar adenoma with a single cyst: A case report.

Alveolar adenoma is a rare and benign pulmonary tumor, which originates from type II pneumocytes and is often incidentally identified on radiographic images. Alveolar adenoma presents as a peripleural, solitary and cystic nodule in the lung and may mimic other types of lung tumors, thus rendering its differential diagnosis difficult. Alveolar adenoma is diagnosed based on histopathological and immunohistochemical analyses. The present study describes the case of a 50-year-old male patient with alveolar adenoma. He visited a local doctor ~3 years prior due to left chest pain. A chest computed tomography scan revealed a cystic lesion in segment 8 of the left lung. A nodular shadow appeared in the cyst and gradually increased in size; the patient was thus referred to the authors' hospital. The nodule was well-defined, solitary and solid; thus, lung cancer or aspergilloma were suspected. Thoracoscopic wedge resection was performed as diagnostic therapy. The frozen sections were non-diagnostic, and a pathological examination revealed an alveolar adenoma with no evidence of malignancy and a negative culture. The patient had a good post-operative course, with no sign of recurrence at the follow-up evaluation 46 months later. On the whole, alveolar adenoma is a rare, benign pulmonary tumor that is difficult to diagnose pre-operatively.

Allyl isothiocyanate and 6-(methylsulfinyl) hexyl isothiocyanate contents vary among wild and cultivated wasabi (Eutrema japonium).

Wasabi (Japanese horseradish, Eutrema japonicum) is the only cultivated species in the genus Eutrema with functional components that provide a strong pungent flavor. To evaluate genetic resources for wasabi breeding, we surveyed variations in the two most abundant isothiocyanate (ITC) components in wasabi, allyl isothiocyanate (AITC) and 6-methylsulfinyl (hexyl) isothiocyanate (6-MSITC, hexaraphane). We also examined the phylogenetic relationships among 36 accessions of wild and cultivated wasabi in Japan using chloroplast DNA analysis. Our results showed that (i) the 6-MSITC content in currently cultivated wasabi accessions was significantly higher than in escaped cultivars, whereas the AITC content was not significantly different. (ii) Additionally, the 6-MSITC content in cultivated wasabi was significantly lower in the spring than during other seasons. This result suggested that the 6-MSITC content responds to environmental conditions. (iii) The phylogenetic position and the 6-MSITC content of accessions from Rebun, Hokkaido Prefecture had different profiles compared with those from southern Honshu, Japan, indicating heterogeneity of the Rebun populations from other Japanese wasabi accessions. (iv) The total content of AITC and 6-MSITC in cultivated wasabi was significantly higher than that of wild wasabi. In conclusion, old cultivars or landraces of wasabi, "zairai", are the most suitable candidates for immediate use as genetic resources.

Standardized Classification of Lung Adenocarcinoma Subtypes and Improvement of Grading Assessment Through Deep Learning.

The histopathologic distinction of lung adenocarcinoma (LADC) subtypes is subject to high interobserver variability, which can compromise the optimal assessment of patient prognosis. Therefore, this study developed convolutional neural networks capable of distinguishing LADC subtypes and predicting disease-specific survival, according to the recently established LADC tumor grades. Consensus LADC histopathologic images were obtained from 17 expert pulmonary pathologists and one pathologist in training. Two deep learning models (AI-1 and AI-2) were trained to predict eight different LADC classes. Furthermore, the trained models were tested on an independent cohort of 133 patients. The models achieved high precision, recall, and F1 scores exceeding 0.90 for most of the LADC classes. Clear stratification of the three LADC grades was reached in predicting the disease-specific survival by the two models, with both Kaplan-Meier curves showing significance (P = 0.0017 and 0.0003). Moreover, both trained models showed high stability in the segmentation of each pair of predicted grades with low variation in the hazard ratio across 200 bootstrapped samples. These findings indicate that the trained convolutional neural networks improve the diagnostic accuracy of the pathologist and refine LADC grade assessment. Thus, the trained models are promising tools that may assist in the routine evaluation of LADC subtypes and grades in clinical practice.

Decrease in the expression of muscle-specific miRNAs, miR-133a and miR-1, in myoblasts with replicative senescence.

Muscles that are injured or atrophied by aging undergo myogenic regeneration. Although myoblasts play a pivotal role in myogenic regeneration, their function is impaired with aging. MicroRNAs (miRNAs) are also involved in myogenic regeneration. MiRNA (miR)-1 and miR-133a are muscle-specific miRNAs that control the proliferation and differentiation of myoblasts. In this study, we determined whether miR-1 and miR-133a expression in myoblasts is altered with cellular senescence and involved in senescence-impaired myogenic differentiation. C2C12 murine skeletal myoblasts were converted to a replicative senescent state by culturing to a high passage number. Although miR-1 and miR-133a expression was largely induced during myogenic differentiation, expression was suppressed in cells at high passage numbers (passage 10 and/or passage 20). Although the senescent myoblasts exhibited a deterioration of myogenic differentiation, transfection of miR-1 or miR-133a into myoblasts ameliorated cell fusion. Treatment with the glutaminase 1 inhibitor, BPTES, removed senescent cells from C2C12 myoblasts with a high passage number, whereas myotube formation and miR-133a expression was increased. In addition, primary cultured myoblasts prepared from aged C57BL/6J male mice (20 months old) exhibited a decrease in miR-1 and miR-133a levels compared with younger mice (3 months old). The results suggest that replicative senescence suppresses muscle-specific miRNA expression in myoblasts, which contributes to the senescence-related dysfunction of myogenic regeneration.

Application of Teeth in Toxicological Analysis of Decomposed Cadavers Using a Carbamazepine-Administered Rat Model.

In a regular autopsy, blood and organs are used to quantify drug and toxicant concentrations; however, specimens such as blood cannot be collected from highly decomposed corpses, making the quantification of drug and toxicants impossible. This study aimed to estimate the blood carbamazepine (CBZ) concentration from teeth, a part of the human body that is best preserved after death. We sampled teeth and blood of rats administered CBZ. The correlation between the tooth and serum CBZ concentrations was analyzed. Rats were euthanized after CBZ administration and kept at 22 °C for 0 to 15 days before sampling the teeth and measuring the CBZ concentration. Undecalcified, fresh, frozen sections of rat teeth were prepared, and CBZ localization was evaluated. CBZ concentrations in both teeth and cardiac blood peaked at 60 min after administration and increased in a dose-dependent manner. CBZ concentration in teeth did not substantially change after death, with high CBZ distribution being observed in the pulp cavity. The tooth and serum CBZ concentrations were highly correlated, suggesting that the measurement of toxicant concentration in sampled teeth would allow for the estimation of blood toxicant concentration in highly decomposed corpses.

Overcoming the Interobserver Variability in Lung Adenocarcinoma Subtyping: A Clustering Approach to Establish a Ground Truth for Downstream Applications.

CONTEXT.­: The accurate identification of different lung adenocarcinoma histologic subtypes is important for determining prognosis but can be challenging because of overlaps in the diagnostic features, leading to considerable interobserver variability. OBJECTIVE.­: To provide an overview of the diagnostic agreement for lung adenocarcinoma subtypes among pathologists and to create a ground truth using the clustering approach for downstream computational applications. DESIGN.­: Three sets of lung adenocarcinoma histologic images with different evaluation levels (small patches, areas with relatively uniform histology, and whole slide images) were reviewed by 17 international expert lung pathologists and 1 pathologist in training. Each image was classified into one or several lung adenocarcinoma subtypes. RESULTS.­: Among the 4702 patches of the first set, 1742 (37%) had an overall consensus among all pathologists. The overall Fleiss κ score for the agreement of all subtypes was 0.58. Using cluster analysis, pathologists were hierarchically grouped into 2 clusters, with κ scores of 0.588 and 0.563 in clusters 1 and 2, respectively. Similar results were obtained for the second and third sets, with fair-to-moderate agreements. Patches from the first 2 sets that obtained the consensus of the 18 pathologists were retrieved to form consensus patches and were regarded as the ground truth of lung adenocarcinoma subtypes. CONCLUSIONS.­: Our observations highlight discrepancies among experts when assessing lung adenocarcinoma subtypes. However, a subsequent number of consensus patches could be retrieved from each cluster, which can be used as ground truth for the downstream computational pathology applications, with minimal influence from interobserver variability.

Pentobarbital overdose: A case of contract killing.

Suicides by pentobarbital overdose have increased since about 2012, which appear to be influenced by technical information on active euthanasia that has spread over the Internet. We encountered a pentobarbital poisoning case of a patient with amyotrophic lateral sclerosis. A caregiver found the patient unconscious immediately after two visitors left the room. The patient was immediately transferred to the emergency hospital but eventually declared dead. A fatal concentration of pentobarbital was detected in peripheral blood samples collected in the emergency hospital and during autopsy (53.8 µg/mL and 29.4 µg/mL, respectively). Because the ratios of pentobarbital concentrations between the gastric contents and peripheral blood were 35 and 29 in the hospital and autopsy samples, respectively, it is likely that pentobarbital was administered via the gastrostomy tube. The patient had contacted the visitors through social media. Although the patient had requested the doctor perform active euthanasia and expressed a desire to end their life on social media, nobody had noticed the plan to commit suicide.

Bortezomib is an effective enhancer for chemical probe-dependent superoxide detection.

Various chemical probes for the detection of reactive oxygen species have been developed to examine oxidative stress associated with different pathologies. L-012, a luminol-based chemiluminescent probe, is widely used to detect extracellular superoxide because of its high sensitivity. We herein demonstrated that the co-application of the peptide boronic acid proteasome inhibitor, bortezomib, with L-012 significantly increased its luminescence without affecting the background. More than a 5-fold increase was detected in the total luminescence of L-012 in both NADPH oxidase-expressing cells and the xanthine oxidase-dependent cell-free superoxide generation system, but not in their background. Therefore, bortezomib increased the signal-to-background ratio and improved the detection of low levels of superoxide. The application of MLN2238, another peptide boronic acid proteasome inhibitor, also enhanced the luminescence of L-012. In contrast, carfilzomib, an epoxyketone proteasome inhibitor, did not increase luminescence, suggesting that the effects of bortezomib depend on the chemical structure of the peptide boronic acid, but not on its pharmacological effects. Bortezomib-induced enhancements appeared to be specific to the detection of superoxide because the detection of H2O2 by Amplex Red/HRP was not affected by the application of bortezomib. In the quantitative detection of the superoxide-specific oxidative product 2-hydroxyethidium (2-OH-E+), the application of bortezomib resulted in a 2-fold increase in the level of 2-OH-E+. Therefore, bortezomib sensitizes the detection of superoxide in both cell-based and cell-free systems, highlighting a novel feature of compounds containing the peptide boronic acid as powerful enhancers for the detection of superoxide.

Primary Pancreatic Mantle Cell Lymphoma Diagnosed via Endoscopic Ultrasound-Guided Fine-Needle Aspiration.

Primary pancreatic lymphomas (PPLs) are rare, and the histological classification of these tumors is difficult. To accurately diagnose and determine the appropriate treatment for PPLs, sufficient sample amounts are necessary. Here, we report a 73-year-old man with a primary pancreatic mantle cell lymphoma. Histological samples were obtained via endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). The tumor cells predominantly composed of atypical small to medium round cells, with diffuse immunoreactivity of CD20 and cyclin D1. In addition, immunoglobulin gene H chain rearrangement was detected. The patient underwent chemotherapy, resulting in complete remission. Eight years after the initiation of chemotherapy, the patient was still alive. EUS-FNA could be a useful and safe diagnostic modality for PPLs by providing enough samples for testing.

Rapid infusion of excessive phenytoin: A newborn autopsy case.

The patient was a two-day-old female infant. The patient's mother was a primigravid in her 20 s who developed premature abruption of the normal placenta on the first day of the 33rd week of gestation. The infant was born by emergency cesarean section with severe neonatal asphyxia with a birth weight of 1928 g. Spontaneous circulation was returned 11 min after birth. The infant was treated under mechanical ventilation in the neonatal intensive care unit, and phenobarbital was administered for repeated seizures. On day 2, spontaneous respiration was observed; however, the patient developed seizures repeatedly. The dose of phenobarbital reached the maximum and was switched to midazolam. In the early morning of day 3, while midazolam was administered up to the maximum dose, the infant developed status epilepticus, and the anticonvulsant drug was changed to phenytoin. Due to a calculation error, the intravenous administration of phenytoin was started at 400 mg/30 min, which is 10-fold of the normal dose. Six minutes later, after 80 mg was administered, the administration was stopped due to a drop in blood pressure; however, the infant died of cardiac arrest. An autopsy, which was performed approximately 25 h after death, revealed the blood phenytoin concentration in the heart was 63.85 µg/mL. The cause of death was determined to be acute phenytoin toxicity. This is the first fatal case reported of the blood concentration of phenytoin caused by rapid intravenous administration.

Anomalous systemic arterial supply to the basal segment of the lung with giant aberrant artery: a case report.

BACKGROUND: Anomalous systemic arterial supply to the basal segment of the lung (ABLL) is a relatively rare congenital anomaly characterized by aberrant systemic arterial blood flow to the basal segment of the lung. We experienced a rare presentation of ABLL, in which a giant aberrant artery with the same dimensions as that of the descending aorta flowed from the celiac artery to left lower lobe. CASE PRESENTATION: An otherwise healthy 42-year-old man was referred to our department due to an abnormal chest X-ray. Enhanced computed tomography revealed a huge and winding aberrant artery with mural thrombus originating from the celiac artery and perfusing into the left lower lobe. We diagnosed giant ABLL and considered possible concomitant pulmonary arteriovenous fistula. The diameter of the aberrant artery was > 30 mm and high-pressure flow was assumed; therefore, we performed staged resection of the left lower lobectomy including division of the aberrant artery at the pulmonary ligament and subsequent embolization of the remnant arterial flow uneventfully. Pathologically, the aberrant artery was abundant with elastic fibers, and dissections of the tunica media and mural thrombus were observed; however, arteriovenous fistula was not confirmed. At 6 postoperative months, enhanced computed tomography showed the aberrant artery to be completely occluded without any symptoms. CONCLUSIONS: We present a case of ABLL that was successfully managed by surgical resection of the left lower lobe with most of the giant aberrant artery and subsequent embolization of the remnant portion. Our study demonstrates that a staged surgical therapy is an acceptable approach for ABLL in case of complication with a giant aberrant artery.

Presence of heat shock protein 47-positive fibroblasts in cancer stroma is associated with increased risk of postoperative recurrence in patients with lung cancer.

BACKGROUND: Heat shock protein 47 (HSP47), a collagen-binding protein, has a specific role in the intracellular processing of procollagen production. HSP47 expression is associated with cancer growth and metastasis in several types of cancers. However, none of the studies have assessed whether HSP47 expression is associated with the risk of postoperative recurrence of lung cancer until now. Therefore, we aimed to assess this association. METHODS: The study population consisted of a cohort of consecutive patients who underwent surgery for lung cancer at Nagasaki University Hospital, Nagasaki, Japan, from January 2009 to December 2010. Patient characteristics, survival and disease-free survival (DFS), and laboratory findings were compared between patients who tested positive and negative for HSP47 expression in lung cancer cells and between those who showed high and low numbers of HSP47-positive fibroblasts in cancer stroma. RESULTS: A total of 133 patients underwent surgery for lung cancer. Sixty-seven patients (50.4%) had HSP47-positive cancer cells, and 91 patients (68.4%) had a higher number of HSP47-positive fibroblasts. The patients with a high number of HSP47-positive fibroblasts had a shorter DFS than those with a low number of HSP47-positive fibroblasts. Multivariate analysis identified only the presence of a high number of HSP47-positive fibroblasts as an independent risk factor for recurrence of lung cancer after surgery (odds ratio, 4.371; 95% confidence interval, 1.054-29.83; P = 0.042). CONCLUSION: The present study demonstrated that the presence of a high number of HSP47-positive fibroblasts in the cancer stroma was a risk factor for recurrence of lung cancer after surgery.

Prognostic impact of mucin spread, tumor cell spread, and invasive size in invasive mucinous adenocarcinoma of the lung.

OBJECTIVES: The pathological T descriptor of lung invasive mucinous adenocarcinoma (IMA) is currently defined according to mucin spread, whereas that of lung non-mucinous adenocarcinoma is defined according to invasive lesion. This study aimed to evaluate and compare the prognostic impact of mucin spread, tumor cell spread, and invasive lesion in patients with lung IMA. MATERIALS AND METHODS: Twenty-seven patients with completely resected pT1-4N0M0 IMA were evaluated. The radiological size (RS), mucin spread size (MS), tumor cell spread size (TS), and invasive size (IS) of the primary tumors were determined. Cox proportional hazards models were used to estimate recurrence-free survival (RFS). Because the MS, TS, and IS may be mutually confounding factors, they were evaluated using separate multivariate models including potential prognostic factors identified as significant on univariate analyses. RESULTS: The median postoperative follow-up time was 4.9 years. TS and IS were significantly smaller than RS by a median of 0.3 cm (p = 0.027) and 1.4 cm (p < 0.0001), whereas MS and RS were not significantly different (p > 0.999). Univariate analyses identified T descriptors defined by MS, TS, and IS as potentially negative prognostic factors, in addition to age >75 years and carcinoembryonic antigen >5 ng/mL. Multivariate analyses revealed that T factors defined by MS, TS, and IS were significant predictors of RFS (p < 0.0001, p = 0.0002, and p = 0.0067, respectively). CONCLUSION: MS is a reasonable determinant of the pathological T descriptor of lung IMA. TS and IS are potential candidates, although they remain discordant with RS. If the TS or IS is to be considered a candidate for the pathological T descriptor of lung IMA, the discordance with RS should first be resolved. If IS is used to define pathological T factor, clear criteria for mucinous AIS/MIA with IMA features should be developed.

Simple, Frequent Indicator for Personal Identification-Postmortem and Antemortem Abdominal Computed Tomography Findings of a Charred Body.

Postmortem personal identification in forensic science is performed using various methods. However, severely burnt bodies are hard to identify using odontological or skeletal features because of carbonization, and sometimes DNA profiling is impracticable because of the unavailability of the relatives. We present a case of a burn victim found after a house fire. Personal identification was attempted, but the body was heavily charred to the bones and the use of physical appearance was impracticable. There were no known relatives or personal belongings of the deceased for comparison of DNA typing. We obtained a series of abdominal computed tomography (CT) scans taken antemortem and found bilateral multiple renal cysts, left renal artery calcification, and a big right inguinal hernia, which matched the deceased's postmortem CT findings and autopsy findings. To date, studies of identification by CT have acted for a rise in precision, but they require complicated calculation or high graphical methods. Calcification of the arteries or renal cysts seen in our case are very common lesions present in many adults with abundant variation; thus, they may be helpful as simple indicators for identification.

Postmortem plasma pentraxin 3 is a useful marker of fatal acute coronary syndrome.

Pentraxin 3 (PTX3) is an acute-phase protein that belongs to the pentraxin superfamily. Recently, many clinical studies have demonstrated that plasma PTX3 concentrations rapidly increase in patients with the acute coronary syndrome (ACS). The aim of this study was to evaluate the forensic utility of postmortem plasma PTX3 as a marker of fatal ACS. We compared the plasma PTX3 concentration in cadavers with suspected fatal ACS to that exhibited in control cases (e.g., asphyxia and immediate death due to a fatal injury). The ACS groups included a coronary stenosis group, which exhibited apparent coronary stenosis, but an absence of coronary thrombi, a coronary thrombi group with thrombi found in the coronary artery, and a group of myocardial rupture following an acute myocardial infarction. The plasma PTX3 concentration was significantly higher in the coronary thrombi group than the control group and other ACS groups. The postmortem plasma PTX3 concentration was higher than the clinical reference values, which appeared to be caused by a postmortem release from circulating neutrophils. In conclusion, although the clinical reference value cannot be applied to postmortem samples, the postmortem plasma PTX3 concentration may be a useful marker of death occurring immediately after the onset of fatal ACS.

Autoerotic asphyxia using a plastic bag loosely covering the head over a gas mask.

Autoerotic death is defined as the accidental death of an individual while masturbating, caused by a device or material used to enhance the sexual response. Here we report an autopsy case of autoerotic death and review the literature. A healthy, single, 33-year-old Japanese male was found dead in his room in a prone position. He was wearing a used gas mask and a plastic bag over his head; the opening of that bag was loosely secured around the neck with a belt. He had no underwear beneath his upper and lower work clothes and the zipper of his pants was open. Adult magazines and DVDs featuring male subjects and other adult toys were found in his room. Images of people wearing gas masks and rubber suits, as well as of individuals whose whole bodies were tied with ropes, were discovered on his personal computer. Records of purchasing full-body tights were also found. Lesions and injuries that could have caused his death were not found in the autopsy or in any of the various examinations. The cause of death was determined to be suffocation assumed to be caused by the plastic bag covering the mask's ventilation. Suicide and homicide were ruled out based on the police investigation of the scene of the victim's death and the attendant circumstances and environment. The death was thus determined to be an accident. We see no major differences in the feature of autoerotic death between Japanese cases and those in the Western countries.

Comparison of postmortem butane distribution between two fatal butane poisoning cases.

Fatal accidents during butane abuse frequently occur in Japan and in many countries around the world. Although analytical data about butane concentration in postmortem samples is being accumulated, when using the data to determine the cause of death, careful interpretation is required because the gas is easily diffused. Two fatal butane poisoning cases were encountered, and butane quantification of autopsy samples obtained from left and right heart blood, femoral blood, kidney, liver, lung, brain and fatty tissues was performed. In both cases, butane concentration in the left heart blood was lower than in the right heart blood or the femoral blood, despite gas inhalation. These findings may indicate that the deceased individuals interrupted gas inhalation and inhaled room air immediately before their death, therefore ruling out asphyxia due to anoxia as the mechanism of death. Case 1, which was suspected to be a not acute death, showed a very high butane concentration ratio of fatty tissues to femoral blood of over 70. Case 2 was considered an acute death, and the butane concentration ratio of fatty tissues to femoral blood was 8.2. These results are consistent with previously reported findings showing that much higher ratios of fatty tissues to blood are compatible with long survival time. In conclusion, the comparison of butane concentration among different samples, including left heart blood versus right heart blood and fatty tissues versus blood, is useful when interpreting the result of postmortem butane analysis to examine the mechanism of death and survival time.

5-HT2A Receptor Agonist-Induced Hyperthermia Is Induced via Vasoconstriction by Peripheral 5-HT2A Receptors and Brown Adipose Tissue Thermogenesis by Peripheral Serotonin Loss at a High Ambient Temperature.

Recreational drugs such as 3,4-methylenedioxymethamphetamine and cocaine induce hyperthermia, which is affected by ambient temperature. 2-(4-Bromo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine (25B-NBOMe), a selective agonist of 5-HT2A receptor used as a recreational drug, reportedly induces hyperthermia. This study aimed to verify whether 25B-NBOMe induces ambient temperature-dependent hyperthermia and to clarify its mechanism. Eight-week-old male Sprague-Dawley rats were administered intraperitoneal injection of 25B-NBOMe at an ambient temperature of 23°C or 29°C. 25B-NBOMe administration at 23°C did not change the core body temperature of the rats, whereas administration at 29°C induced significant hyperthermia 30-120 minutes postadministration. Tail surface temperature temporarily decreased 30 minutes postadministration, indicating heat storage by peripheral vasoconstriction despite a high ambient temperature. Because 25B-NBOMe-induced-hyperthermia was suppressed by sarpogrelate, but not by destruction of central noradrenaline or serotonin neurons, peripheral 5-HT2A receptors were considered contributors to the development of hyperthermia at a high ambient temperature, independently from central neurons. The temperature of brown adipose tissue (BAT) increased 60-120 minutes postadministration of 25B-NBOMe at 29°C, indicating thermogenesis. Previous studies have reported that peripheral serotonin contributes to the inhibition of BAT thermogenesis. Decreased plasma serotonin levels were observed at 29°C, and serotonin administration partially suppressed 25B-NBOMe-induced hyperthermia at a high ambient temperature, suggesting that decreased levels of peripheral serotonin induced BAT thermogenesis. Our findings indicate that 25B-NBOMe induces hyperthermia at a high ambient temperature via vasoconstriction regulated by 5-HT2A receptors and BAT thermogenesis mediated by decreased levels of plasma serotonin. Thus, peripheral serotonin plays a partial but important role in thermoregulation.

Update on Rare Idiopathic Interstitial Pneumonias and Rare Histologic Patterns.

CONTEXT: - In 2013, the revised American Thoracic Society and European Respiratory Society classification of idiopathic interstitial pneumonias (IIPs) described 2 rare IIPs and 2 rare histologic patterns. Because of the rarity of the disease, there is limited evidence related to the histology. Because the rare histologic patterns are provisional criteria, no unanimous consensus on histologic diagnostic criteria has yet been reached. OBJECTIVE: - To review the histologic features for rare IIPs and rare histologic patterns, and to provide diagnostic aids and discuss the differential diagnosis. DATA SOURCES: - Published peer-reviewed literature and the authors' personal experience. CONCLUSIONS: - Following the publication of the international consensus classification, evidence regarding rare IIPs and rare histologic patterns has accumulated to some extent, although to date the amount remains insufficient and further evidence is required. Because the diagnosis is sometimes challenging, a multidisciplinary approach represents the gold standard in reaching an accurate diagnosis for these rare disorders.