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Groundwater-level changes after earthquakes provide insight into changes in hydrogeological properties such as permeability and pore pressure. Quantifying such changes, both their location and magnitude, is usually hindered by limited data. Using extensive high-resolution water-level monitoring records, we provide direct evidence of significant groundwater drawdown (4.74-m maximum) over a 160-km2 area along crustal ruptures after the Mw 7.0, 2016, Kumamoto earthquake. Approximately 106 m3 of water disappeared within 35 min after the main shock. The loss of water was not caused by static-strain driven pore-pressure decrease nor by releasing of water through structural pathways, but most likely by water transfer downwards through open cracks. Such changes may impact the security of water resources, the safety of underground waste repositories, and contaminant transport in seismically active areas.

Processing bodies (P-bodies, PBs) are cytoplasmic foci formed by condensation of translationally inactivated messenger ribonucleoprotein particles (mRNPs). Infection with the protozoan parasite Trypanosoma cruzi (T. cruzi) promotes PB accumulation in host cells, suggesting their involvement in host mRNA metabolism during parasite infection. To identify PB-regulated mRNA targets during T. cruzi infection, we established a PB-defective human fibrosarcoma cell line by knocking out the enhancer of mRNA decapping 4 (EDC4), an essential component of PB assembly. Next-generation sequencing was used to establish transcriptome profiles for wild-type (WT) and EDC4 knockout (KO) cells infected with T. cruzi for 0, 3, and 24 h. Ingenuity pathway analysis based on the differentially expressed genes revealed that PB depletion increased the activation of several signaling pathways involved in the innate immune response. The proinflammatory cytokine IL-1β was significantly upregulated following infection of PB-deficient KO cells, but not in WT cells, at the mRNA and protein levels. Furthermore, the rescue of PB assembly in KO cells by GFP-tagged wild-type EDC4 (+WT) suppressed IL-1β expression, whereas KO cells with the C-terminal-deleted mutant EDC4 (+Δ) failed to rescue PB assembly and downregulate IL-1β production. Our results suggest that T. cruzi assembles host PBs to counteract antiparasitic innate immunity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

5-Aminolevulinic acid (5-ALA), a non-proteinogenic amino acid, is an intermediate in the biosynthesis of heme and exerts antiviral effects against feline coronavirus (FCoV); however, the underlying mechanisms remain unclear. In the biosynthesis of heme, 5-ALA is condensed and converted to protoporphyrin IX (PpIX), which is then transformed into heme by the insertion of ferrous iron. Previous research has suggested that the metabolites generated during heme biosynthesis contribute to the antiviral effects of 5-ALA. Therefore, the present study investigated the in vitro mechanisms responsible for the antiviral effects of 5-ALA. The results obtained revealed that 5-ALA and PpIX both effectively reduced the viral titer in the supernatant of FCoV-infected fcwf-4 cells. Moreover, PpIX exerted virucidal effects against FCoV. We also confirmed that 5-ALA increased PpIX levels in cells. While hemin induced heme oxygenase-1 gene expression, it did not reduce the viral titer in the supernatant. Sodium ferrous citrate decreased PpIX levels and suppressed the antiviral effects of 5-ALA. Collectively, these results suggest that the antiviral effects of 5-ALA against FCoV are dependent on PpIX.

Chromosomal 2q37 deletion syndrome, marked by developmental delays, distinctive facial features, and a spectrum of congenital anomalies, presents significant challenges in the cardiac management of affected individuals. This paper details the case of an 8-month-old male with 2q37 deletion syndrome, manifesting atrial and ventricular septal defects, patent ductus arteriosus, and right ventricular outflow tract stenosis, leading to a demanding postoperative course. Despite an initially stable post-surgery phase, the onset of junctional ectopic tachycardia necessitated prolonged veno-arterial extracorporeal membrane oxygenation support, highlighting the syndrome's potential for intricate postoperative courses. The complexities encountered in this case, including extended renal replacement therapy and delayed thoracic closure, underscore the syndrome's multisystem impact and the critical need for tailored, multidisciplinary care approaches. This report contributes to the growing body of knowledge on the cardiac implications of 2q37 deletion syndrome, emphasising the importance of individualised surgical strategies and the ongoing exploration of genotype-phenotype correlations in this rare genetic disorder.

Laparoscopic surgery has been used to treat gastric submucosal tumors (SMTs). Laparoscopic and endoscopic cooperative surgery (LECS) has been used when subtotal resection has been difficult, which enabled resection of these tumors. In this study, we reviewed the medical records of patients with gastric SMTs who underwent laparoscopic surgery in our hospital with the aim of reporting the surgical indications, procedures (especially for LECS), and outcomes of surgery. This study involved 55 patients who underwent laparoscopic surgery between April 2014 and March 2021. We classified the patients into two groups: laparoscopy-assisted surgery group (non-LECS group, n = 30) and LECS group (n = 25). LECS was performed in the upper stomach, in the greater curvature of the lower stomach, and in both intraluminal and intramural locations in the middle stomach. Non-LECS was selected for extraluminal and intramural tumors in the greater curvature of the upper stomach. There were no severe complications associated with the operation. There was one postoperative complication in the LECS group. The length of postoperative hospital stay did not significantly differ between the LECS and non-LECS groups. We reported the surgical procedures for gastric SMTs in our hospital. It is essential to make full use of the multiple techniques reported in this article and examine the location of the tumor to avoid excess or insufficient resection. Our review of the present case series allowed us to select the appropriate surgical approach for gastric SMTs based on the lesion location and type of development., (© 2024. The Author(s).)

A new polyketide, cladoic acid, was isolated from a fungus of the genus Cladosporium . The structure of the highly oxygenated trans -decalin ring with an all- E triene side chain was elucidated by extensive spectroscopic analysis. The unique chair/twist-boat conformation of the trans -decalin core and the flexibility of the B-ring were demonstrated by computer-aided conformational analysis. Cladoic acid was active against Trypanosoma cruzi and inhibited the proliferation of amastigotes and epimastigotes with IC 50 values of 27 and 46 μM, respectively, but it did not show any appreciable activity against P388 murine leukemia cells, bacteria, or fungi, indicating it is a potential candidate for drug development against Chagas disease.

A search for anti-trypanosomal natural compounds from plants collected in El Salvador, a country particularly endemic for Chagas disease, resulted in the isolation of five lignan-type compounds ( 1 - 5 ) from Peperomia pseudopereskiifolia . The lignan derivatives 1 , 2 , and 4 are new. Their absolute configuration was determined by chemical derivatization. Compounds 1 , 5 , 6 , and 8 exhibited anti-trypanosomal activity against the amastigote form of T. cruzi comparable to that of the existing drug benznidazole.

Background: Esophageal submucosal tumors (SMTs) are rare, occurring in less than 1% of esophageal neoplasms. For surgical treatment of esophageal SMTs, enucleation is usually the procedure of choice for benign tumors. This study aimed at evaluating the surgical technique and outcomes of thoracoscopic enucleation with esophagoscopy for esophageal SMTs. Methods: Patients with esophageal SMTs who underwent thoracoscopic enucleation between 2015 and 2022 were retrospectively investigated. Surgery was performed with the patient in the prone position. First, an esophagoscope was inserted, and a sodium hyaluronate solution with indigo carmine dye was injected into the submucosal layer just below the tumor. Next, under thoracoscopy, the tumor was exposed through a thoracoscopic incision and dissection of the muscularis propria and adventitia was performed at the tumor site. The colored layer resulting from the previously injected dye was identified, and tumor enucleation was performed under guidance of the dye so as not to damage the mucosa or pseudocapsule. Results: In total, 5 surgeries were performed. The mean operative time was 122.6 minutes (range 84-168 minutes), mean blood loss was 21.1 mL (range 0-80 mL), and mean postoperative hospital stay was 8 days (range 7-10 days). There were no postoperative complications. Pathological diagnosis revealed 2 cases of gastrointestinal stromal tumors, 2 cases of schwannoma, and 1 case of leiomyoma. Conclusions: We believe that this technique is a useful and safe method of performing thoracoscopic enucleation of esophageal SMTs because the injected dye provides an indicator of the resection line during enucleation.

Endotracheal intubation (ETI) is a common and crucial intervention. Whether the performance of ETI differs according to the sex of the laryngoscopist remains unclear. The aim of this study was to assess sex disparities in markers of ETI performance among novices using a high-fidelity simulator. This prospective observational study was conducted from April 2017 to March 2019 in a public medical university. In total, 209 medical students (4th and 5th grade) without clinical ETI experience were recruited. Of the 209 students, 64 (30.6%) were female. The participants used either a Macintosh direct laryngoscope or C-MAC video laryngoscope in combination with a stylet or gum-elastic bougie to perform ETI on a high-fidelity simulator. The primary endpoint was the maximum force applied on the maxillary incisors during laryngoscopy. The secondary endpoint was the time to ETI. The implanted sensors in the simulator automatically quantified the force and time to ETI. The maximum force applied on the maxillary incisors was approximately 30% lower in the male than female group for all laryngoscopes and intubation aids examined (all P < 0.001). Similarly, the time to ETI was approximately 10% faster in the male than female group regardless of the types of laryngoscopes and intubation aids used (all P < 0.05). In this study, male sex was associated with a lower maximum force applied on the maxillary incisors during both direct and indirect laryngoscopy performed by novices. A clinical study focusing on sex differences in ETI performance is needed to validate our findings.

Chagas disease, a neglected tropical disease caused by the protozoan Trypanosoma cruzi poses a significant health challenge in rural areas of Latin America. The current pharmacological options exhibit notable side effects, demand prolonged administration, and display limited efficacy. Consequently, there is an urgent need to develop drugs that are safe and clinically effective. Previously, we identified a quinone compound (designated as compound 2) with potent antiprotozoal activity, based on the chemical structure of komaroviquinone, a natural product renowned for its antitrypanosomal effects. However, compound 2 was demonstrated considerably unstable to light. In this study, we elucidated the structure of the light-induced degradation products of compound 2 and probed the correlation between the quinone ring's substituents and its susceptibility to light. Our findings led to the discovery of quinones with significantly enhanced light stability, some of which exhibiting antitrypanosomal activity. The most promising compound was evaluated for drug efficacy in a mouse model of Chagas disease, revealing where a notable reduction in blood parasitemia.

This study presented the first attempt to detect precursory changes in groundwater level before the 2016 Kumamoto Earthquake. This detection was achieved by accurately determining the relationship between long-term groundwater level fluctuation and crustal deformation over 16 years through analysis of groundwater level time-series data acquired at 17 sites within the study area. Here, we show that the observed groundwater levels were lower than the modelled levels in aquifers composed of porous strata (Togawa lava and part of the pre-Aso volcanic rocks), and that there were larger differences until 2014, which diminished until the occurrence of the Kumamoto Earthquake. The initial reduction in the modelled groundwater level and the latter recovery were most likely caused by crustal strain relaxation associated with the large 2011 earthquake off the Pacific coast of Tohoku (M w 9.0) and the strain accumulation prior to the 2016 Kumamoto Earthquake., (© 2023. The Author(s).)

Background: Chagas disease can lead to life-threatening cardiac manifestations. Regional factors, including genetic characteristics of circulating Trypanosoma cruzi (T. cruzi), have attracted attention as likely determinants of Chagas disease phenotypic expression and Chagas cardiomyopathy (CCM) progression. Our objective was to elucidate the differential transcriptomic signatures of cardiomyocytes resulting from infection with genetically discrete T. cruzi strains and explore their relationships with CCM pathogenesis and progression., Methods: HL-1 rodent cardiomyocytes were infected with T. cruzi trypomastigotes of the Colombian, Y, or Tulahuen strain. RNA was serially isolated post-infection for microarray analysis. Enrichment analyses of differentially expressed genes (fold-change ≥ 2 or ≤ 0.5) highlighted over-represented biological pathways. Intracellular levels of reactive oxygen species (ROS) were compared between T. cruzi-infected and non-infected HL-1 cardiomyocytes., Results: We found that oxidative stress-related gene ontology terms (GO terms), 'Hypertrophy model', 'Apoptosis', and 'MAPK signaling' pathways (all with P < 0.01) were upregulated. 'Glutathione and one-carbon metabolism' pathway, and 'Cellular nitrogen compound metabolic process' GO term (all with P < 0.001) were upregulated exclusively in the cardiomyocytes infected with the Colombian/Y strains. Mean intracellular levels of ROS were significantly higher in the T. cruzi-infected cardiomyocytes compared to the non-infected (P < 0.0001)., Conclusions: The upregulation of oxidative stress-related and hypertrophic pathways constitutes the universal hallmarks of the cardiomyocyte response elicited by T. cruzi infection. Nitrogen metabolism upregulation and glutathione metabolism imbalance may implicate a relationship between nitrosative stress and poor oxygen radicals scavenging in the unique pathophysiology of Chagas cardiomyopathy., (© 2023. The Author(s).)

Objective: Computed tomography (CT)-guided lipiodol marking is one of the targeting methods for resecting small pulmonary nodules or ground-glass nodules in video-assisted thoracic surgery (VATS). However, lipiodol spreading during marking has not been assessed, practically. In this study, we examined the clinical significance and the influence of lipiodol spreading on surgery., Methods: From April 2010 to March 2021, 176 pulmonary nodules in 167 patients were marked with lipiodol under CT guided before VATS. The marking images after lipiodol injection were classified into "Spread" and "non-Spread." Lung resection was sequentially performed on the same day., Results: All target nodules were successfully resected in VATS. In the classification of marking images, Spread was 32 (18%), non-Spread was 144 (82%). There was a significant difference in duration of surgery (mean; 138.7 min vs. 118.3 min, p = 0.0496) and amount of bleeding (mean; 32.7 g vs. 11.2 g, p = 0.0173). Provided that limited to the data of wedge resections without intrathoracic pleural adhesion (n = 117), there was no significant difference in duration of surgery (mean; 104.8 min vs. 99.6 min, p = 0.48), amount of bleeding (mean; 4.9 g vs. 5.3 g, p = 0.58). In the multivariate logistic regression analysis, the risk factor of lipiodol spreading was intrathoracic pleural adhesion (odds ratio: 3.16, 95% confidence interval: 1.12-8.97, p = 0.03). There was no relationship between marking image and complication rate., Conclusions: Lipiodol spreading did not directly influence surgery and complication. However, it was a sign of intrathoracic pleural adhesion, which could lead to increased duration of surgery and amount of bleeding., (© 2022. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

Background/aim: The effectiveness of transanal total mesorectal excision (Ta-TME) in extended surgery (ES) has been discussed. This study examined the short-term outcomes of the first 31 patients who underwent Ta-TME after its introduction and verified the safety of Ta-TME in ES in the early stage following its introduction., Patients and Methods: Thirty-one consecutive patients who underwent Ta-TME between December 2021 and January 2023 at our institution were included. The indications for Ta-TME were rectal tumors that could be palpated during rectal examination and bulky tumors that were deemed unresectable without Ta-TME. Short-term outcomes were retrospectively compared between patients who underwent normal Ta-TME, (n=27, TME group) and patients who underwent ES beyond TME (n=4, ES group). The data are shown as the median and interquartile range. Statistical analysis was performed with the Mann-Whitney U-test and Fisher's exact test., Results: Total pelvic exenteration (TPE) was performed in the 4 th and 8 th patients; the 9 th patient underwent a combined resection of the right adnexa and urinary bladder wall. The 31 st patient underwent a combined resection of the uterus and the right adnexa. The operative time was 353 [285-471] vs. 569 [411-746] min for the TME and ES groups (p=0.039). Blood loss was 8 [5-40] vs. 45 [23-248] ml (p=0.065); postoperative hospital stay was 15 [10-19] vs. 11 [9-15] days (p=0.201); postoperative complications (higher than grade III) were 5 (19%) vs. 0 (p=1.000). Negative CRM was achieved in all cases., Conclusion: Ta-TME in ES was as safe as normal Ta-TME in the early stage after its introduction., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

UV absorption spectroscopy-guided fractionation of the culture extract of a marine obligate bacterium of the genus Microbulbifer yielded a novel cyclic hexapeptide, bulbiferamide ( 1 ). NMR spectroscopic and mass spectrometric analyses revealed the structure of 1 to be a cyclic tetrapeptide appending a ureido-bridged two amino acid unit. Notably, Trp is a junction residue, forming on one hand a very rare N -aminoacylated indole linkage for cyclization and on the other hand connecting the ureido-containing tail structure, which is an unprecedented way of configuring peptides. The component amino acids were determined to be l by the advanced Marfey's method. Compound 1 displayed growth inhibitory activity against Trypanosoma cruzi epimastigotes with an IC 50 value of 4.1 μM, comparable to the currently approved drug benznidazole, while it was not cytotoxic to P388 murine leukemia cells at 100 μM.

The coronavirus disease 2019 (COVID-19) has significantly affected the mental health of healthcare workers (HCWs). The authors have provided psychosocial support to HCWs working in typical hospitals and nursing homes in Fukushima Prefecture, Japan, where major COVID-19 outbreaks have occurred since December 2020. This study retrospectively examines depressive symptoms before psychosocial interventions among HCWs working at typical hospitals and nursing homes experiencing in-house major COVID-19 outbreaks. We have offered psychosocial support in eight hospitals and nursing homes, obtaining data on the mental health status of 558 HCWs using the Patient Health Questionnaire-9. The study's results indicate that 29.4% of HCWs have exhibited moderate or higher depressive symptoms, and 10.2% had suicidal ideation. Multiple logistic regression analysis showed that being a nurse was associated with higher depressive symptoms and suicidal ideation compared to other HCWs. In addition, multiple logistic regression analysis of Polymerase Chain Reaction-positive HCWs showed that being a nurse and the number of COVID-19-related symptoms was associated with high depressive symptoms. These results suggest that HCWs in typical hospitals and nursing homes experiencing major COVID-19 outbreaks are more likely to exhibit severe depressive symptoms, which may worsen if infected with COVID-19. This study's findings expand the current understanding of HCWs' depressive symptoms and the importance of psychosocial support during unexpected major outbreaks in healthcare facilities.

Groundwater‐level changes after earthquakes provide insight into changes in hydrogeological properties such as permeability and pore pressure. Quantifying such changes, both their location and magnitude, is usually hindered by limited data. Using extensive high‐resolution water‐level monitoring records, we provide direct evidence of significant groundwater drawdown (4.74‐m maximum) over a 160‐km2 area along crustal ruptures after the Mw 7.0, 2016, Kumamoto earthquake. Approximately 106 m3 of water disappeared within 35 min after the main shock. The loss of water was not caused by static‐strain driven pore‐pressure decrease nor by releasing of water through structural pathways, but most likely by water transfer downwards through open cracks. Such changes may impact the security of water resources, the safety of underground waste repositories, and contaminant transport in seismically active areas. Key Points: Groundwater levels changed immediately after the 2016 Mw 7.0 Kumamoto earthquakeSurface and aquifer waters were transferred into the deeper crust through rupture systemsProposed water drawdown model may be transferrable globally to other aquifer systems [ABSTRACT FROM AUTHOR]