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An 80-year-old man underwent rectal resection and insertion of a central venous catheter through the left subclavian vein 16 years earlier. Following surgery, he developed edema of his left upper limb that became exacerbated and infected. Computed tomography showed occlusion of the subclavian vein and multiple arteriovenous shunts from the branches of the axillary artery to the venous sac of the axillary vein. Angiography confirmed numerous shunts between the branches of the axillary artery and vein and dilated collateral veins. Embolization of the venous sac was performed using coils, alcohol, and glue. Postprocedural angiography showed complete eradication of the nidus.

Campeche, one of the Spanish Empire's main Mexican ports, was a place where previously distinct cultures and populations intermingled during the colonial era (AD 1540-1680). Investigation of the town's central plaza revealed a Hispanic cemetery of multi-ethnic burials. The authors combine previous analyses with newly generated genome-wide data from 10 individuals to trace detailed life histories of the mostly young, local Indigenous Americans and first-generation European and African immigrants, none of whom show evidence of genetic admixture. These results provide insights into the individual lives and social divides of the town's founder communities and demonstrate how ancient DNA analyses can contribute to understanding early colonial encounters. Keywords: Mexico, Campeche, Novohispanic society, ancient DNA, isotope analysis, genomics, Introduction Following their arrival in 1519, the Spanish conquistadors took less than two years to conquer Aztec central Mexico; however, it took a further two decades to secure their rule [...]

Abstract. Introduction:. Previous studies on chemotherapy-induced peripheral neuropathy (CIPN) have focused on neuronal damage. Although some studies have revealed that the fascia is an important sensory organ, currently, we do not know about chemotherapy drug-induced fascial dysfunction. Objectives:. This study aimed to explore the fascia as a nonneural cause of mechanical hypersensitivity in CIPN by investigating the expression of hyaluronic acid synthase (HAS) and histology of the fascia in an animal model of CIPN. Methods:. Rats were intraperitoneally administered with vincristine (VCR). Mechanical hypersensitivities of the hind paw and the anterior tibial muscle were assessed. The expression of HAS mRNA in the fascia of the anterior tibial muscles was quantitated using reverse transcription polymerase chain reaction. Immunohistochemistry was also performed for HAS2, hyaluronic acid–binding protein, and S100A4 in the fascia. Results:. Vincristine administration significantly decreased mechanical withdrawal thresholds in the hind paw and the anterior tibial muscle after day 3. Quantitative polymerase chain reaction showed significant downregulation of HAS mRNAs in the fascia of VCR-treated rats. Immunohistochemical analysis showed that the number of cells with strong HAS2 immunoreactivity, classified as fasciacytes by morphology and colocalized marker S100A4, decreased significantly in the VCR group. Conclusion:. Hyaluronic acid plays a critical role in somatic pain sensation. Damaged fascia could be a possible cause of musculoskeletal pain in patients with CIPN. This study suggests that fascia is a nonneural cause and novel therapeutic target for chemotherapy-induced “peripheral neuropathy.”

Summary:. One of the complications of anal surgery or disease is anal stenosis. To release the tension of the anus, a tension-releasing incision in the perianal skin and various anoplasty procedures are usually considered. The aim of this article is to describe a straightforward technique with local flaps for severe anal stenosis after anal reconstruction. A 57-year-old man presented to the clinic with diverticulitis secondary to severe anal stenosis, and reported difficulty with defecation after perianal skin resection around the anus and surgery to create a V-Y advancement flap for perianal primary Paget disease 9 months previously. After improvement of the diverticulitis using antibiotics, bilateral transposition flaps were transferred to release the anal stenosis. The surgical treatment for severe anal stenosis has been known to entail several complications, including infection, incontinence, anal mucosal ectropion, pruritus, wound dehiscence, and restenosis. In this severe case, because the scars were situated at the 6 o’clock and 12 o’clock positions on the anus due to the previous V-Y advancement flap, bilateral rotation flaps were transferred from the 3 o’clock and 9 o’clock positions of the anus to prevent wound dehiscence and partial flap necrosis. Three months later, the size of the anus was unchanged, but additional surgery was performed at the patient’s request. A bilateral transposition flap procedure was used, with flaps designed and elevated from the 6 o’clock and 12 o’clock positions. The postoperative course was uneventful, and the anal stenosis was improved.

Summary: Neutrophils play a critical role in the eradication of Pseudomonas aeruginosa, a major pathogen causing lung infection. However, the mechanisms used by the pathogen to evade neutrophil-mediated killing remain poorly understood. Using a high-density transposon screen, we find that P. aeruginosa colonization in the lung is promoted by pathogen nitrite reductase nirD. nirD is required for ammonia production from nitrite, a metabolite derived from nitrogen oxide (NO) generated by inducible NO synthetase (iNOS) in phagocytes. P. aeruginosa deficient in nirD exhibit reduced survival in wild-type neutrophils but not in iNOS-deficient neutrophils. Mechanistically, nirD enhances P. aeruginosa survival in neutrophils by inhibiting the localization of the pathogen in late phagosomes. P. aeruginosa deficient in nirD show impaired lung colonization after infection in wild-type mice but not in mice with selective iNos deficiency in neutrophils. Thus, P. aeruginosa uses neutrophil iNOS-mediated NO production to limit neutrophil pathogen killing and to promote its colonization in the lung.

Transient receptor potential families play important roles in the pathology of osteoarthritis (OA) of the knee. While transient receptor potential ankyrin 1 (TRPA1) is also an essential component of the pathogenesis of various arthritic conditions, its association with pain is controversial. Thus, we researched whether TRPA1 is involved in knee OA pain by in vivo patch–clamp recordings and evaluated the behavioral responses using CatWalk gait analysis and pressure application measurement (PAM). Injection of the Trpa1 agonist, allyl isothiocyanate (AITC), into the knee joint significantly increased spontaneous excitatory synaptic current (sEPSC) frequency in the substantia gelatinosa of rats with knee OA, while injection of the Trpa1 antagonist, HC-030031, significantly decreased the sEPSC. Meanwhile, AITC did not affect the sEPSC in sham rats. In the CatWalk and PAM behavioral tests, AITC significantly decreased pain thresholds, but no difference between HC-030031 and saline injections was observed. Our results indicate that Trpa1 mediates knee OA-induced pain. We demonstrated that Trpa1 is activated in the knee joints of rats with OA, and Trpa1 activity enhanced the pain caused by knee OA.

Abstract The prognostic impact of direct‐acting antivirals (DAAs) on patients with hepatitis C‐related hepatocellular carcinoma (C‐HCC) is still unclear. This study aimed to evaluate the prognosis of C‐HCC in the DAA era. We enrolled 1237 consecutive patients with treatment‐naive C‐HCC who underwent radical radiofrequency ablation between 1999 and 2019. We also enrolled 350 patients with nonviral HCC as controls. We divided these patients into three groups according to the year of initial treatment: 1999–2005 (cohort 1), 2006–2013 (cohort 2), and 2014–2019 (cohort 3). The use of antiviral agents and their effect in patients with C‐HCC was investigated. Overall survival was evaluated for each cohort using the Kaplan‐Meier method and a multivariable Cox proportional hazards regression model. Sustained virologic response (SVR) was achieved in 52 (10%), 157 (26%), and 102 (74%) patients with C‐HCC in cohorts 1–3, respectively. The 3‐ and 5‐year survival rates of patients with C‐HCC were 82% and 59% in cohort 1; 80% and 64% in cohort 2; and 86% and 78% in cohort 3, respectively (p = 0.003). Multivariable analysis adjusted for age, liver function, and tumor extension showed that the prognosis of C‐HCC improved in cohort 3 compared to cohort 1 (adjusted hazard ratio [aHR], 0.49; 95% confidence interval [CI], 0.32–0.73; p

Abstract Evaluation of feasibility and safety of percutaneous radiofrequency ablation using bipolar radiofrequency devices in a prospective multicenter cohort of patients with benign aldosterone-producing adenoma. A total of five institutions participated. CT-guided percutaneous RFA was performed for patients diagnosed as APA. The safety of the procedure was evaluated using the Common Terminology Criteria for Adverse Events. During the 84-day follow-up period, serial changes in plasma aldosterone concentration and plasma renin activity were measured. The percentage of patients with normalized hormonal activity after the procedure, was calculated with 95% confidence intervals. Forty patients were enrolled, and two patients were excluded for cerebral hemorrhage and no safe puncture root. In another patients, RFA was tried, but an intraprocedural intercostal arterial injury occurred. Consequently, RFA was completed in thirty-seven patients (20 men, 17 women; mean age, 50.4 ± 10.0 year). The tumor size was 14.8 ± 3.8 mm. The treatment success rate of the ablation was 94.6% (35/37), and a 2nd session was performed in 2.7% (1/37) patients. Grade 4 adverse events were observed in 4 out of 38 sessions (10.5%). The normalization of plasma aldosterone concentration or aldosterone-renin ratio was 86.5% (72.0–94.1: 95% confidence interval) on day 84. Percutaneous CT-guided RFA for APA using a bipolar radiofrequency system was safe and feasible with clinical success rate of 86.5% on day 84.

Abstract Caspase‐generated fragmented cytokeratin 18 (fCK18) is recognized as a useful noninvasive biomarker in the diagnosis of nonalcoholic fatty liver disease (NAFLD), particularly nonalcoholic steatohepatitis (NASH). However, fCK18 measurement is not applied clinically due to widely variable cut‐off values under the current enzyme‐linked immunosorbent assay platform. Therefore, we developed a highly sensitive chemiluminescent enzyme immunoassay using newly developed monoclonal antibodies against fCK18 and investigated its relevance in NASH diagnosis. Serum fCK18 levels were measured in the derivation and validation cohort. The correlation between serum fCK18 levels and NAFLD activity score (NAS), fibrosis stage, and liver function was examined. Serum fCK18 levels were significantly correlated with alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma‐glutamyl transpeptidase. Serum fCK18 levels were significantly associated with NAS, Brunt's grade/stage, Matteoni's classification, portal inflammation, and fat accumulation in the liver. Notably, hepatocyte ballooning was the only independent variable significantly associated with serum fCK18 in the multivariate linear regression analysis. Serum fCK18 levels were significantly elevated in patients with NAFLD and nonalcoholic fatty liver (NAFL) compared to healthy individuals. They were also significantly elevated in patients with NAFL compared to NASH defined by NAS or Matteoni's classification, with area under the curve values being 0.961 (NAFLD vs. healthy), 0.913 (NAFL vs. healthy), 0.763 (NASH vs. NAFL), and 0.796 (NASH type 3–4 vs. NAFL type 1–2). These results were confirmed by a validation cohort. Notably, changes over time in serum fCK18 levels were significantly correlated with changes in ALT, AST, and the fibrosis‐4 index in 25 patients who underwent lifestyle modification. Serum fCK18 levels were significantly correlated with liver damage associated with NASH pathology. Serum fCK18 levels are accurate in distinguishing patients with NAFL or NASH from healthy individuals and may be useful to monitor NASH over time.

Objective: This study aimed to introduce and evaluate a novel software-based system, BioTrace, designed for real-time monitoring of thermal ablation tissue damage during image-guided radiofrequency ablation for hepatocellular carcinoma (HCC). Methods: BioTrace utilizes a proprietary algorithm to analyze the temporo-spatial behavior of thermal gas bubble activity during ablation, as seen in conventional B-mode ultrasound imaging. Its predictive accuracy was assessed by comparing the ablation zones it predicted with those annotated by radiologists using contrast-enhanced computed tomography (CECT) 24 hours post-treatment, considered the gold standard. The study included 20 liver tumors. Results: The median tumor measurement along the major axis was 1.2 cm. The median Dice coefficient, Sensitivity, and Precision between BioTrace and CECT were 0.90, 0.91, and 0.91, respectively. The intraclass correlation showed excellent agreement in volume size between BioTrace and CECT findings (0.98). Conclusion: BioTrace effectively generates an ablation damage prediction map based on real-time ultrasound imaging, accurately predicting the ablation zone as confirmed by 24-hour post-procedural CECT. This system has the potential to enhance the safety and efficacy of ablation procedures in clinical settings. [ABSTRACT FROM AUTHOR]

Oxygen isotope ratios (δ18O) of tree-ring cellulose and historical documentary records are widely used to explore the hydroclimatic conditions of the past. In this study, we attempted to reconstruct chronologies of local climate disasters spanning 4 centuries in central Japan using these proxy data. For tree-ring δ18O measurements, we prepared cellulose samples from a long-living cedar tree with continuously broad ring widths. To enhance the temporal resolution, we divided each annual ring into several (mainly six) segments. Analysis of the correlations with observed relative humidity and precipitation data revealed that the intra-ring δ18O variations in the sample tree reflected the hydroclimatic conditions from April to July in each year. Subsequently, we chronologically listed the occurrence of eight types of disasters in the 17th to 19th centuries in the area adjacent to the sample tree according to 20 titles of "Town/City history", which is a compilation of historical documentary records from the local municipality. By comparison with the intra-ring δ18O data, we found that most of the major droughts and long rains recorded in the historical documents occurred in the Baiu rainy season (typically June–July) or pre-Baiu season, corresponding to the growing season of the sample tree. Based on an analysis of the intra-ring δ18O variation for documentary-based drought and long-rain years, we set thresholds of intra-ring δ18O values to identify and extract drought and long-rain years. Drought and long-rain chronologies obtained by applying these thresholds were temporally continuous, complementing those based on documentary records. They depicted the relationships between the frequency of these climate disasters and the occurrence of major famines and the long-term tendency of length and magnitude of the Baiu rainy season in historical times. [ABSTRACT FROM AUTHOR]

We examined the epitaxial growth of Ge _1− _x Sn _x thin film with x ∼ 0.50 on GaSb(111) substrate using a low-temperature MBE. X-ray diffraction and Raman scattering spectroscopy analyses revealed that the Ge _1− _x Sn _x thin film with x ∼ 0.50 with no strain was successfully grown on GaSb(111). Furthermore, in the Raman analysis, a sharper Ge-Sn peak compared to Ge-Ge and Sn-Sn peaks was clearly observed and showed an improved thermal stability than Ge _1− _x Sn _x with a smaller Sn composition. This suggests that the Ge _1− _x Sn _x with x ∼ 0.50 would have an ordered Ge–Sn bonding like a zinc blend system, that is significantly different from Si _1− _x Ge _x case.

BackgroundAutoantibodies against glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) cause chylomicronemia by blocking the ability of GPIHBP1 to bind lipoprotein lipase (LPL) and transport the enzyme to its site of action in the capillary lumen.ObjectiveA patient with multiple sclerosis developed chylomicronemia during interferon (IFN) β1a therapy. The chylomicronemia resolved when the IFN β1a therapy was discontinued. Here, we sought to determine whether the drug-induced chylomicronemia was caused by GPIHBP1 autoantibodies.MethodsWe tested plasma samples collected during and after IFN β1a therapy for GPIHBP1 autoantibodies (by western blotting and with enzyme-linked immunosorbent assays). We also tested whether the patient's plasma blocked the binding of LPL to GPIHBP1 on GPIHBP1-expressing cells.ResultsDuring IFN β1a therapy, the plasma contained GPIHBP1 autoantibodies, and those autoantibodies blocked GPIHBP1's ability to bind LPL. Thus, the chylomicronemia was because of the GPIHBP1 autoantibody syndrome. Consistent with that diagnosis, the plasma levels of GPIHBP1 and LPL were very low. After IFN β1a therapy was stopped, the plasma triglyceride levels returned to normal, and GPIHBP1 autoantibodies were undetectable.ConclusionThe appearance of GPIHBP1 autoantibodies during IFN β1a therapy caused chylomicronemia. The GPIHBP1 autoantibodies disappeared when the IFN β1a therapy was stopped, and the plasma triglyceride levels fell within the normal range.

Coil embolization is widely performed for pulmonary arteriovenous malformations (PAVMs). We describe herein 2 cases of hemoptysis during long-term follow-up after coil embolization for PAVMs. For both cases, lobectomy was performed and histopathological examinations revealed chronic inflammation and bronchial epithelium extension into the sac of the PAVM. In addition, we performed a systematic review of previous reports of hemoptysis after embolization for PAVMs.

Diverting stoma (DS) is widely created in colorectal surgery. High-output stoma (HOS) is a major complication of DS, which can lead to dehydration and thrombosis. Additionally, antiphospholipid syndrome (APS) is a risk factor for thrombosis, and it rarely occurs in men. Herein, we describe a case of multiple thromboses caused by chronic dehydration after HOS. A 48-year-old man visited our hospital with fever and lower abdominal pain; he was diagnosed with sigmoid diverticulitis. He underwent laparoscopic high anterior resection for relapsing diverticulitis and diverting ileostomy during the same operation. On postoperative day 1, an output of 3,000 mL/day was observed from the ileostomy. The stoma output exceeded 2,000 mL/day, which was diagnosed as HOS, and chronic dehydration persisted despite supplementation and restriction of oral water intake. Three months postoperatively, a computed tomography scan before ileostomy closure showed multiple thrombi in the inferior vena cava, right common iliac vein, and pulmonary artery. After antithrombotic therapy, ileostomy closure was performed. As lupus anticoagulant was positive twice and APS was diagnosed, antithrombotic therapy was changed from warfarin to direct oral anticoagulants. Thrombosis did not recur 6 months postoperatively. This is the first report of a case wherein APS was present in the background of thrombosis caused by HOS or chronic dehydration. It is important to be cautious about APS when there is thrombosis after HOS to select appropriate therapeutic agents.

Abstract Background The Master’s double two-step test (MDT), which is used to screen for coronary heart disease, is difficult for physically impaired patients to complete. The purpose of this study was to clarify the relationship between the results of the MDT and prognosis after lung cancer surgery. Methods Between May 2004 and September 2019, 1,434 patients underwent complete resection for lung cancer at our hospital. Among them, 418 with pathological stage I disease who underwent lobectomy were evaluated. We defined patients who could accomplish the MDT as the complete MDT group and those who could not as the incomplete MDT group. Patients who could not perform the MDT due to physical problems were included in the incomplete MDT group. We explored the prognostic impact of the MDT results in these patients. Results Fifty-three patients (12.7%) were in the incomplete MDT group; compared with the complete MDT group, they were older and had poorer performance status and respiratory function. However, the incidence of postoperative complications and 90-day mortality did not differ significantly between groups. Multivariate analyses revealed that age (p

Abstract Background Post-extubation dysphagia (PED) is recognized as a common complication in the intensive care unit (ICU). Speech and language therapy (SLT) can potentially help improve PED; however, the impact of the timing of SLT initiation on persistent PED has not been well investigated. This study aimed to examine the timing of SLT initiation and its effect on patient outcomes after extubation in the ICU. Methods We conducted this multicenter, retrospective, cohort study, collecting data from eight ICUs in Japan. Patients aged ≥ 20 years with orotracheal intubation and mechanical ventilation for longer than 48 h, and those who received SLT due to PED, defined as patients with modified water swallowing test scores of 3 or lower, were included. The primary outcome was dysphagia at hospital discharge, defined as functional oral intake scale score

We report genome-wide ancient DNA from 49 individuals forming four parallel time transects in Belize, Brazil, the Central Andes, and the Southern Cone, each dating to at least ∼9,000 years ago. The common ancestral population radiated rapidly from just one of the two early branches that contributed to Native Americans today. We document two previously unappreciated streams of gene flow between North and South America. One affected the Central Andes by ∼4,200 years ago, while the other explains an affinity between the oldest North American genome associated with the Clovis culture and the oldest Central and South Americans from Chile, Brazil, and Belize. However, this was not the primary source for later South Americans, as the other ancient individuals derive from lineages without specific affinity to the Clovis-associated genome, suggesting a population replacement that began at least 9,000 years ago and was followed by substantial population continuity in multiple regions.

Detection of analytes by means of field-effect transistors bearing ligand-specific receptors is fundamentally limited by the shielding created by the electrical double layer (the "Debye length" limitation). We detected small molecules under physiological high-ionic strength conditions by modifying printed ultrathin metal-oxide field-effect transistor arrays with deoxyribonucleotide aptamers selected to bind their targets adaptively. Target-induced conformational changes of negatively charged aptamer phosphodiester backbones in close proximity to semiconductor channels gated conductance in physiological buffers, resulting in highly sensitive detection. Sensing of charged and electroneutral targets (serotonin, dopamine, glucose, and sphingosine-1-phosphate) was enabled by specifically isolated aptameric stem-loop receptors.

Aptamers are chemically synthesized oligonucleotides or peptides with molecular recognition capabilities. We investigated recognition of substrate-tethered small-molecule targets, using neurotransmitters as examples, and fluorescently labeled DNA aptamers. Substrate regions patterned via microfluidic channels with dopamine or   l-tryptophan were selectively recognized by previously identified dopamine or l-tryptophan aptamers, respectively. The on-substrate dissociation constant determined for the dopamine aptamer was comparable to, though, slightly greater than the previously determined solution dissociation constant. Using prefunctionalized neurotransmitter-conjugated oligo(ethylene glycol) alkanethiols and microfluidics patterning, we produced multiplexed substrates to capture and to sort aptamers. Substrates patterned with l-3,4-dihydroxyphenylalanine, l- threo-dihydroxyphenylserine, and l-5-hydroxytryptophan enabled comparison of the selectivity of the dopamine aptamer for different targets via simultaneous determination of in situ binding constants. Thus, beyond our previous demonstrations of recognition by protein binding partners (i.e., antibodies and G-protein-coupled receptors), strategically optimized small-molecule-functionalized substrates show selective recognition of nucleic acid binding partners. These substrates are useful for side-by-side target comparisons and future identification and characterization of novel aptamers targeting neurotransmitters or other important small molecules.

Interactions between small molecules and biomolecules are important physiologically and for biosensing, diagnostic, and therapeutic applications. To investigate these interactions, small molecules can be tethered to substrates through standard coupling chemistries. While convenient, these approaches co-opt one or more of the few small-molecule functional groups needed for biorecognition. Moreover, for multiplexing, individual probes require different surface functionalization chemistries, conditions, and/or protection/deprotection strategies. Thus, when placing multiple small-molecules on surfaces, orthogonal chemistries are needed that preserve all functional groups and are sequentially compatible. Here, we approach high-fidelity small-molecule patterning by coupling small-molecule neurotransmitter precursors, as examples, to monodisperse asymmetric oligo(ethylene glycol)alkanethiols during synthesis and prior to self-assembly on Au substrates. We use chemical lift-off lithography to singly and doubly pattern substrates. Selective antibody recognition of pre-functionalized thiols was comparable to or better than recognition of small molecules functionalized to alkanethiols after surface assembly. These findings demonstrate that synthesis and patterning approaches that circumvent sequential surface conjugation chemistries enable biomolecule recognition and afford gateways to multiplexed small-molecule functionalized substrates.

Serotonin-based nanoparticles represent a class of previously unexplored multifunctional nanoplatforms with potential biomedical applications. Serotonin, under basic conditions, self-assembles into monodisperse nanoparticles via autoxidation of serotonin monomers. To demonstrate potential applications of polyserotonin nanoparticles for cancer therapeutics, we show that these particles are biocompatible, exhibit photothermal effects when exposed to near-infrared radiation, and load the chemotherapeutic drug doxorubicin, releasing it contextually and responsively in specific microenvironments. Quantum mechanical and molecular dynamics simulations were performed to interrogate the interactions between surface-adsorbed drug molecules and polyserotonin nanoparticles. To investigate the potential of polyserotonin nanoparticles for in vivo targeting, we explored their nano-bio interfaces by conducting protein corona experiments. Polyserotonin nanoparticles had reduced surface-protein interactions under biological conditions compared to polydopamine nanoparticles, a similar polymer material widely investigated for related applications. These findings suggest that serotonin-based nanoparticles have advantages as drug-delivery platforms for synergistic chemo- and photothermal therapy associated with limited nonspecific interactions.