Quantification of collagen fiber properties in alcoholic liver fibrosis using polarization-resolved second harmonic generation microscopy.

Liver fibrosis is assessed mainly by conventional staining or second harmonic generation (SHG) microscopy, which can only provide collagen content in fibrotic area. We propose to use polarization-resolved SHG (PR-SHG) microscopy to quantify liver fibrosis in terms of collagen fiber orientation and crystallization. Liver samples obtained from autopsy cases with fibrosis stage of F0-F4 were evaluated with an SHG microscope, and 12 consecutive PR-SHG images were acquired while changing the polarization azimuth angle of the irradiated laser from 0° to 165° in 15° increments using polarizer. The fiber orientation angle (φ) and degree (ρ) of collagen were estimated from the images. The SHG-positive area increased as the fibrosis stage progressed, which was well consistent with Sirius Red staining. The value of φ was random regardless of fibrosis stage. The mean value of ρ (ρ-mean), which represents collagen fiber crystallinity, varied more as fibrosis progressed to stage F3, and converged to a significantly higher value in F4 than in other stages. Spatial dispersion of ρ (ρ-entropy) also showed increased variation in the stage F3 and decreased variation in the stage F4. It was shown that PR-SHG could provide new information on the properties of collagen fibers in human liver fibrosis.

Artificial intelligence-based forensic sex determination of East Asian cadavers from skull morphology.

Identification of unknown cadavers is an important task for forensic scientists. Forensic scientists attempt to identify skeletal remains based on factors including age, sex, and dental treatment remains. Forensic scientists commonly consider skull or pelvic shape to evaluate the sex; however, these evaluations require sufficient experience and knowledge and lack objectivity and reproducibility. To ensure objectivity and reproducibility for sex evaluation, we applied a gated attention-based multiple-instance learning model to three-dimensional (3D) skull images reconstructed from postmortem head computed tomography scans. We preprocessed the images, trained with 864 training data, validated the model with 124 validation data, and evaluated the performance of our model in terms of accuracy with 246 test data. Furthermore, three forensic scientists evaluated the 3D skull images, and their performances were compared with those of the model. Our model showed an accuracy of 0.93, which was higher than that of the forensic scientists. Our model primarily focused on the entire skull owing to visualization but focused less on the areas often investigated by forensic scientists. In summary, our model may serve as a supportive tool to identify cadaver sex based on skull shape. Further studies are required to improve the model's performance.

Variations in echolocation click characteristics of finless porpoise in response to day/night and absence/presence of vessel noise.

Small odontocetes produce echolocation clicks to feed and navigate, making it an essential function for their survival. Recently, the effect of vessel noise on small odontocetes behavior has attracted attention owing to increase in vessel activities; however, the effects of the surrounding environmental factor, vessel noise, and day/night on echolocation click characteristics have not been well studied. Here, we examined the effects of vessel noise and day/night on variations in echolocation clicks and click trains parameters. Passive acoustic monitoring of on-axis echolocation clicks produced by free-ranging finless porpoises (Neophocaena asiaeorientalis sunameri) was performed at two sites in Japan, Seto Inland Sea and Mikawa Bay, in June-September 2021 and March-August 2022, using A-tag and SoundTrap 300HF. Generalized Linear Model was used to elucidate the effect of vessel noise, day/night, and surrounding environmental factors (water temperature, synthetic flow velocity, and noise level) on echolocation click and click train parameters. Echolocation click and click train parameters were strongly affected by day/night, whereas the absence/presence vessel noise did not exhibit statistically significant influence. Particularly, -3 dB bandwidth was wider, click duration was shorter, and inter-click intervals in a train were shorter at night, which may facilitate information processing at night, thereby compensating for the lack of visual information. The interaction between day/night and the absence/presence of vessel noise affected the source level of finless porpoises, with higher levels observed in the absence of vessel noise during the daytime compared to other conditions at the site with low vessel traffic. Overall, these results suggest that echolocation clicks by finless porpoise were likely to fluctuate to adapt with surrounding complex environmental conditions, especially day/night.

Deep Neural Networks-Based Age Estimation of Cadavers Using CT Imaging of Vertebrae.

Although age estimation upon death is important in the identification of unknown cadavers for forensic scientists, to the best of our knowledge, no study has examined the utility of deep neural network (DNN) models for age estimation among cadavers. We performed a postmortem computed tomography (CT) examination of 1000 and 500 male and female cadavers, respectively. These CT slices were converted into 3-dimensional images, and only the thoracolumbar region was extracted. Eighty percent of them were categorized as training datasets and the others as test datasets for both sexes. We fine-tuned the ResNet152 models using the training datasets. We conducted 4-fold cross-validation, and the mean absolute error (MAE) of the test datasets was calculated using the ensemble learning of four ResNet152 models. Consequently, the MAE of the male and female models was 7.25 and 7.16, respectively. Our study shows that DNN models can be useful tools in the field of forensic medicine.

Fundamental Care's state of knowledge around the world: Where are we now? A scoping review.

AIMS: To investigate and describe the current state of knowledge about Fundamental Care in terms of population, contexts, concepts and gaps. DESIGN: A scoping review. DATA SOURCES: CINAHL, Medline, PsycINFO and EMBASE databases were searched in April 2021 for eligible literature, published from January 2010, onwards. REVIEW METHODS: This scoping review was built around the recommendations of Peters et al. (2020 version). Two researchers conducted the literature search, and three researchers independently screened the titles and abstracts of the retrieved studies' data, using the eligibility criteria and the review questions as a guide. RESULTS: The search yielded 763 records, of which 107 were included. Results are presented under seven subheadings: (a) Countries and Continents, (b) Context, (c) Research Design, (d) Publishing/Journal, (e) Participants and Population, (f) Keywords and (g) Fundamental of Care Framework and Practice Process. All the retrieved articles describe the current state of knowledge about Fundamental Care in terms of population, contexts, concepts and gaps. CONCLUSION: This scoping review highlighted the elevated number of articles that have been published since the beginning of the work on Fundamental Care, 10 years ago. The included articles are related to different dimensions of research, practice and teaching and to the Fundamentals of Nursing Care, but also to nursing theory. Finally, most of the articles had a nursing focus. IMPACT: The results of this scoping review allow us to highlight the work from the past 10 years. This may be of interest to learn more about the research surrounding Fundamental Care. This scoping review allows us to better target the theoretical and empirical developments to focus on in the coming years.

Description of the first acoustic recording of spinner dolphins (Stenella longirostris) from the northern straits of Malacca, Malaysia (L).

Relatively little is known about spinner dolphins in Malaysian waters and the wider Southeast Asian region. This note represents the first known acoustic recording of the species sighted opportunistically in the northern Straits of Malacca. Over a brief 20 min sighting, 46 whistles were recorded and four tonal types were detected, with 54.4% being upsweep whistles. The whistle duration ranged from 36 to 977 ms and the frequency ranged from 6.6 to 23.8 kHz. Fifty-seven click trains with a mean interclick interval of 41.5 ± 19.3 ms were detected. These findings provide a baseline for future regional acoustic research on this species.

An autopsy case of pulmonary artery intimal sarcoma: detailed observation of tumor and its related lesions in pulmonary arteries.

We report an autopsy-proven case of a 33-year-old man who died of intimal sarcoma of the pulmonary artery. A large mass (5×4 cm) occluded the main and bilateral pulmonary arteries. Tumor cell morphology was consistent with that of undifferentiated pleomorphic sarcoma. Comprehensive histological observation of 18 pulmonary arteries from proximal to distal revealed continuous extension of the tumor from the main to the subsegmental arteries along the intima, forming an arteriosclerosis-like intimal thickening. Distal small arteries were also affected by eccentric intimal thickening or recanalization. Lung parenchyma was not involved, although there were two wedge-shaped small pulmonary infarctions caused by tumorous obstruction of the associated arteries. Histological results indicated that the intimal sarcoma in the pulmonary artery, which appeared occlusive with growth limited to the proximal artery, had in fact already spread more peripherally than expected. Both the proximal lesions and the distal small arteries were affected by peripheral tumor emboli or by pulmonary hypertension induced by the proximal tumor. However, as seen in this case, most of the occlusive tumor was located locally and intraluminally, in the proximal artery, and removing the proximal tumor by pulmonary endarterectomy was considered effective for symptomatic improvement.

Two autopsy cases of rupture of the aorta by fistula formation after thoracic endovascular aortic repair and open stent-grafting on aortic arch aneurysm.

The mortality rate of aortic aneurysm/dissection is low in Japan. Two surgical procedures, the thoracic endovascular aortic repair (TEVAR) and the open stent-grafting have contributed much in survival of such aneurysmal patients. We encountered with two autopsy cases of death by aortic rupture with fistula formation after these procedures. Case 1 is an 85-year-old male who had the history of TEVAR for thoracic aorta aneurysm one and a half year before his death. His endovascular stent-graft was composed of a steel endoskeleton consisting of six Z-shape elements while at autopsy, one of the elements locating at the distal part was found inserted deep into the wall of descending aorta, causing aorto-esophageal fistula. Case 2 is an 88-year-old male who had the history of open stent-grafting for aortic aneurysm eight years ago. At autopsy, the stent-graft was found detached from aorta at its lesser curvature, causing gap formation between the aorta and the stent. Six Z-shaped stent elements, the parts of stent-graft, were found separated from descending aorta and located in the aneurism. Furthermore, three of the separated elements were found inserted deep in the aortic wall, causing aorto-pulmonary fistula. Since aorto-esophageal fistula formation after surgery for aortic aneurysm is very rare in TEVAR and there are no reported cases of death by aorto-pulmonary fistula in the open stent-grafting, these cases are reported here.

Liquid chromatography-tandem mass spectrometry detection of benzalkonium chloride (BZK) in a forensic autopsy case with survival for 18 days post BZK ingestion.

We report a forensic autopsy case of an elderly man who ingested unknown amount of germicidal disinfectant containing 50% benzalkonium chloride (BZK). He survived for 18 days after BZK ingestion and then died because of pneumonia. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was used to detect three BZK compounds (C12-BZK, C14-BZK and C16-BZK) in the blood. Extraction of BZK was carried out according to a modified QuEChERS method. Chromatographic separation was achieved on an ODS column and detection was performed in selected reaction monitoring mode. The accuracy and the precision were acceptable for quantitative analysis in the concentration range of 10-200 ng/mL for the three BZK compounds. BZK was detected in heart and femoral vein blood samples even 18 days after BZK ingestion. Taking into consideration clinical information during 18 days hospitalization and the autopsy findings, the cause of death was attributed to BZK poisoning. Several toxico-kinetic factors regarding absorption and excretion of BZK in the body were also discussed to elucidate the detection of BZK such a long time after ingestion.

Reversal of morphine-induced respiratory depression by doxapram in anesthetized rats.

The present study was undertaken to investigate whether doxapram, a blocker of tandem pore K(+) (TASK-1/-3) channels, is a useful tool for recovery from morphine-induced ventilatory disturbances. Spontaneous ventilation and the hind leg withdrawal response against noxious thermal stimulation were recorded simultaneously in anesthetized rats. Morphine (1.0mg/kg, i.v.) decreased the minute volume resulting from depression of the ventilatory rate and tracheal airflow. Concomitantly, it prolonged the latency of withdrawal response against the thermal stimulation. Subsequent intravenous injection of doxapram recovered the morphine-induced ventilatory depression. This effect of doxapram declined rapidly after a single injection (1.0-3.0mg/kg, i.v.) but persisted with a continuous infusion (0.33mg/kg/min). Neither single injection nor continuous infusion of doxapram had any detectable effect on the analgesic potency of morphine. The central respiratory activity was recorded from the phrenic nerve in anesthetized, vagotomized, paralyzed and artificially ventilated rats. Morphine (3.0mg/kg, i.v.) induced respiratory depression, characterized by a prolonged plateau-like inspiratory discharge (apneustic discharge) in the phrenic nerve. Doxapram (10mg/kg, i.v.) restored the morphine-induced apneustic discharge to an augmenting inspiratory discharge. This study demonstrated that doxapram counteracted morphine-induced respiratory depression by stimulating the central respiratory network without compromising morphine antinociception. These results support the clinical use of doxapram for amelioration of ventilatory disturbances in patients treated with opioids.

Mechanisms of pentazocine-induced ventilatory depression and antinociception in anesthetized rats.

This study was performed to clarify mechanisms underlying pentazocine-induced ventilatory depression and antinociception. Spontaneous ventilation and hind leg withdrawal response against nociceptive thermal stimulation were simultaneously recorded in anesthetized rats. Pentazocine decreased minute volume resulting from depression of the ventilatory rate and tracheal airflow, and prolonged the latency of withdrawal response. Pre-treatment of ß-funaltorexamine, but not nor-binaltorphimine, significantly attenuated pentazocine-induced ventilatory depression, while either antagonist weakened its analgesic potency. Comparing with effects of fentanyl and U50488, the present results suggest that ventilatory depression induced by pentazocine is mediated by mainly µ receptors and analgesia by both µ and κ receptors.

Effects of prostaglandin E2 on synaptic transmission in the rat spinal trigeminal subnucleus caudalis.

The spinal trigeminal subnucleus caudalis (Vc) receives preferentially nociceptive afferent signals from the orofacial area. Nociceptive stimuli to the orofacial area induce cyclooxygenase both peripherally and centrally, which can synthesize a major prostanoid prostaglandin E2 (PGE2) that implicates in diverse physiological functions. To clarify the roles of centrally-synthesized PGE2 in nociception, effects of exogenous PGE2 on synaptic transmission in the Vc neurons were investigated in the rat brainstem slice. Spontaneously occurring excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) were recorded, respectively, under pharmacological blockade of inhibitory and excitatory transmission by whole-cell patch-clamp mode. Perfusion of PGE2 (1-5 µM) increased the frequency of sIPSCs in a concentration-dependent manner but had no significant effect on the amplitude. Similarly to the effects on sIPSCs, PGE2 increased the sEPSC frequency without any effect on the amplitude. These facilitatory effects of PGE2 on spontaneous synaptic transmissions were blocked by an EP1 antagonist SC19220 but not by an EP4 antagonist AH23848. Electrical stimulation of the trigeminal tract evoked short latency EPSCs (eEPSCs) in the Vc neurons. PGE2 (5 µM) was ineffective on the eEPSCs. The present study demonstrated that PGE2 facilitated spontaneous synaptic transmissions in the Vc neurons through activating the presynaptic EP1 receptors but had no effect on the trigeminal tract-mediated excitatory transmission. These results suggest that centrally-synthesized PGE2 modifies the synaptic transmission in the Vc region, thereby contributing to the processing of nociceptive signals originated from the orofacial area.

Blockade of phosphodiesterase 4 reverses morphine-induced ventilatory disturbance without loss of analgesia.

AIMS: Ventilatory disturbance is a fatal side-effect of opioid analgesics. Separation of analgesia from ventilatory depression is important for therapeutic use of opioids. It has been suggested that opioid-induced ventilatory depression results from a decrease in adenosine 3',5'-cyclic monophosphate content in the respiratory-related neurons. Therefore, we examined the effects of caffeine, a methylxanthine non-selective phosphodiesterase (PDE) inhibitor with adenosine antagonistic activity, and rolipram, a racetam selective PDE4 inhibitor, on ventilatory depression induced by morphine. MAIN METHODS: Spontaneous ventilation and paw withdrawal responses to nociceptive thermal stimulation were measured in anesthetized rats simultaneously. The efferent discharge of the phrenic nerve was recorded in anesthetized, vagotomized, paralyzed and artificially ventilated rats. KEY FINDINGS: Rolipram (0.1 and 0.3 mg/kg, i.v.) and caffeine (3.0 and 10.0 mg/kg, i.v.) relieved morphine (1.0 mg/kg, i.v.)-induced ventilatory depression but had no discernible effect on its analgesic action. Rolipram (0.3 and 1.0 mg/kg, i.v.) and caffeine (10.0 and 20.0 mg/kg, i.v.) recovered morphine (3.0 mg/kg, i.v.)-induced prolongation and flattening of inspiratory discharge in the phrenic nerve. SIGNIFICANCE: Inhibition of PDE4 may be a possible approach for overcoming morphine-induced ventilatory depression without loss of analgesia.

Modulation of glutamatergic transmission by presynaptic N-methyl-D-aspartate mechanisms in second-order neurons of the rat nucleus tractus solitarius.

The present study investigated the physiological function of presynaptic N-methyl-d aspartate (NMDA) mechanisms in glutamatergic transmission in the rat nucleus tractus solitarius (NTS). Membrane currents were recorded from the NTS second-order neurons by using whole-cell patch pipettes including MK-801 to block postsynaptic NMDA receptors. All experiments were performed under blockade of inhibitory synaptic transmission. Co-application of NMDA and d-serine decreased the tractus solitarius (TS)-evoked excitatory postsynaptic currents (eEPSCs) in 7/12 (58%) of neurons, and increased the paired pulse ratio. The remaining neurons were insensitive to NMDA and d-serine. Application of an NMDA antagonist D-AP5 had no effect on eEPSCs in all 8 neurons tested. Action potential-independent EPSCs (miniature EPSCs; mEPSCs) were recorded in the presence of tetrodotoxin. Co-application of NMDA and d-serine increased the mEPSC frequency but had no significant effect on the amplitude in 5/28 (18%) of neurons. D-AP5 decreased the mEPSC frequency without effect on the amplitude in 6/18 (33%) of neurons. This study demonstrated that (1) NMDA receptors were presynaptically distributed in a subset of NTS second-order neurons and that (2) the presynaptic NMDA receptors played an inhibitory role in TS-mediated release of glutamate and a facilitatory role in spontaneous release of glutamate. The present results suggest that the activation of presynaptic NMDA receptors modulates glutamatergic transmissions in the rat NTS second-order neurons.

Acoustic capture-recapture method for towed acoustic surveys of echolocating porpoises.

Passive acoustic monitoring for cetaceans mainly employ fixed-location methods or point transect samplings; an acoustic survey from a moving platform to conduct line transects is less common. In this study, acoustic capture-recapture by combining a double-observer method with line transect sampling was performed to observe Yangtze finless porpoises. Two acoustic devices were towed with the distance between them varying 0.5 to 89.5 m. The conditional probabilities that both devices would detect the porpoises within the same time window were calculated. In a 1-s time window, it became smaller as the distance between the devices increased, approaching zero when the distance between them was more than 50 m. It was considered that the devices with less than 50 m distance detected the same signals from the same animals, which means the identical detection. When the distance between them is too great, the recapture rate is reduced and the incidence of false matching may increase. Thus, a separation distance of around 50 m between two devices in acoustic capture-recapture of Yangtze finless porpoises was recommended. Note that the performance of the double detections can change depending on the particular device used and on animal behaviors such as vocalizing interval, ship avoidance.