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BACKGROUND: The organized functioning of the anisotropic myocardial layers-including the inner longitudinal, middle circular, and outer longitudinal layers-is essential for stable systemic circulation. However, the proteomic profile of each myocardial layer has not been studied yet. Here, we aimed to elucidate the layer-specific proteomic profile of human cardiac tissue using microscopic sampling. METHODS: Normal hearts were obtained from five autopsy cases, and cardiomyocytes were microdissected separately from the three myocardial layers of the left ventricle. Histological analysis and shotgun proteomic profiling were performed, followed by immunohistochemical analysis. RESULTS: Histologically, no significant changes were observed among the three layers regarding cardiomyocyte diameter and myocardial fibrosis. Totally 1220 proteins-comprising 9404 peptides-were identified from 15 samples, of which the expression levels of 92 proteins were significantly altered among the layers. Gene ontology enrichment analysis revealed that the proteins specifically elevated in the inner and outer layers mostly belonged to the actin filament-binding protein group. In particular, MYH1 was highly expressed in cardiomyocytes in the outer layer, and CTNNA3 was highly expressed at the intercalated disc in the inner layer. CONCLUSIONS: This is the first report on layer-specific proteomic profiling of human normal hearts. Anisotropic profiles of actin filament-binding proteins in myocardial layers may contribute to the anisotropic contractile and conductive abilities of the heart. Knowledge of the layer-specific proteome profiles of a human heart in the normal state can aid in further research on cardiac pathology, such as the prognosis and treatment of focal myocardial infarction.
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Miocárdio , Miócitos Cardíacos , Proteômica , Humanos , Proteômica/métodos , Masculino , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Feminino , Miocárdio/metabolismo , Miocárdio/patologia , Pessoa de Meia-Idade , Proteoma/metabolismo , Proteoma/análise , Adulto , IdosoRESUMO
Cell-penetrating peptides (CPPs) serve as potent vehicles for delivering membrane-impermeable compounds, including nucleic acids, into cells. In a previous study, we reported the successful intracellular delivery of small interfering RNAs (siRNAs) with negligible cytotoxicity using a peptide containing an unnatural amino acid (dipropylglycine). In the present study, we employed the same seven peptides as the previous study to evaluate their efficacy in delivering plasmid DNA (pDNA) intracellularly. Although pDNA and siRNA are nucleic acids, they differ in size and biological function, which may influence the optimal peptide sequences for their delivery. Herein, three peptides demonstrated effective pDNA transfection abilities. Notably, only one of the three peptides previously exhibited efficient gene-silencing effect with siRNA. These findings validate our hypothesis and offer insights for the personalized design of CPPs for the delivery of pDNA and siRNA.
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Peptídeos Penetradores de Células , DNA , Plasmídeos , RNA Interferente Pequeno , Peptídeos Penetradores de Células/química , Humanos , DNA/química , RNA Interferente Pequeno/química , RNA Interferente Pequeno/administração & dosagem , Glicina/química , Transfecção , Células HeLa , Sobrevivência Celular/efeitos dos fármacosRESUMO
Hemophagocytic lymphohistiocytosis (HLH) represents a fatal immunopathology derived from excessive inflammatory reactions. In particular, lymphoma-associated hemophagocytic syndrome (LAHS) is associated with a dismal prognosis. The current study presented a challenging case of splenic LAHS. A 71-year-old man presented with fatigue and anorexia. Laboratory test results revealed anemia, thrombocytopenia, lactate dehydrogenase elevation and markedly elevated levels of ferritin (6,210 ng/ml) and soluble interleukin 2 receptor (sIL-2R; 11,328 U/ml). Abdominal computed tomography revealed marked splenomegaly, while fluorodeoxyglucose positron emission tomography revealed increased tracer uptake in the spleen. An elective splenectomy was performed, which led to the diagnosis of B-cell splenic lymphoma with transformation from indolent to aggressive lymphoma. Prior to the splenectomy, thrombocytopenia and hepatic dysfunction with rapidly progressing jaundice appeared, accompanying further elevation of ferritin (25,197 ng/ml) and sIL-2R levels (30,420 U/ml). On postoperative day 5, the patient was transferred to a tertiary care institution and corticosteroid pulse therapy was immediately initiated after establishing the diagnosis of LAHS. Liver dysfunction gradually recovered and subsequent chemotherapy resulted in complete remission with improved performance status. At eight months after the onset, the patient remains alive without any signs of residual lymphoma. Although splenic lymphoma typically manifests with low-grade lymphoma, it can transform into high-grade lymphoma associated with severe complications, such as HLH and multiple organ failure. In this case, splenectomy assisted in not only establishing the diagnosis but also in tumor cytoreduction before commencing chemotherapy. Through interdisciplinary collaboration, the patient was successfully treated by performing a timely splenectomy, followed by steroid pulse therapy and chemotherapy.
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PURPOSE: Clinically relevant evidence for the timing of starting combination therapy with peritoneal dialysis and hemodialysis remains scarce. We retrospectively examined whether combination therapy during the induction phase of dialysis prolongs peritoneal dialysis duration. METHODS: This retrospective study includes 160 patients who underwent combination therapy from 20 dialysis facilities. Four groups were categorized: combination at peritoneal dialysis induction (n = 12, Proactive combination group), and combination following peritoneal dialysis durations of < 2 years (n = 65), 2-5 years (n = 70), or > 5 years (n = 13). Differences in technique survival of dialysis, mortality, and hospitalization due to cardiovascular events in the groups were observed. RESULTS: The Proactive combination group had the longer mean duration of combination therapy (3.18 years) comparing to that of combination therapy following peritoneal dialysis (1.45 years), but total peritoneal dialysis duration was shorter than in control groups (4.02 years). Of the 160 cases in the entire cohort, there were 8 deaths, 18 ischemic heart disease hospitalizations, and 18 stroke hospitalizations. The Proactive group had lower crude mortality rate (0/12 cases, 0.0%) and crude hospitalization rate for ischemic heart disease (1/11, 8.3%) than the other groups. However, this cohort study did not have enough statistical power to adjust for patients' background, and we were unable to fully examine the differences in such clinical outcomes by the timing of initiation of combination therapy. CONCLUSION: Use of combination therapy in the induction phase might prolong the duration of combination therapy, but is not necessarily effective for prolonging peritoneal dialysis technique survival.
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INTRODUCTION: Shoulder injuries in baseball players cause excessive shoulder load during pitching and scapular dyskinesis (SD). However, the characteristics of pitching kinetics in the shoulder joint with SD are unclear. This study aimed to investigate the effect of SD on pitching kinetics in the shoulder joint of baseball players. METHOD: Seventy-two college and independent league baseball players participated in the study. The pitching motion was measured using an 18-camera motion-capture system. SD was classified into four types (I-IV) using the scapular dyskinesis test (SDT). The pitching kinetics data were analyzed. RESULTS: The agreement of SD in this study was 56/72 (77.8%). SD were classified into 31 abnormal group (type I-â ¢) and 25 control group (type â £). Three participants with measurement failure during the pitching motion analysis were excluded from the analysis. The abnormal group showed a larger maximum value of the glenohumeral normalized anterior joint force than the control group. CONCLUSIONS: These results suggest that an increase in GH anterior force during pitching causes an excessive increase in external rotation of the GH with an insufficient posterior tilt of the scapula with SD. Therefore, baseball pitching with SD may involve shoulder injuries owing to excessive shoulder load during pitching.
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Beisebol , Discinesias , Lesões do Ombro , Articulação do Ombro , Humanos , Ombro , Escápula , Discinesias/etiologiaRESUMO
Stereocontrolled synthesis of rare sugar derivatives, namely α-d-allulofuranosides, was achieved using d-fructose, one of the most abundant carbohydrates in nature. The following are the key steps of the α-d-allulofuranosides' synthesis. (1) An α-selective glycosidation reaction of 1,3,4,6-tetra-O-benzoylated d-fructofuranosyl donor to obtain α-d-fructofuranosides with 98 %-75 % isolated yields. (2) A regioselective 1,4,6-tri-O-pivaloylation reaction of the tetraol of α-d-fructofuranosides with the C3-hydroxy group remaining intact. (3) The oxidation of the C3-hydroxy group followed by the stereoselective reduction of the C3-carbonyl group. Primary and secondary alcohols and sugars can be used as glycosyl acceptors and aglycones for the following pivaloylation and stereoinversion reactions to obtain α-d-allulofuranosides.
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Álcoois , Carboidratos , OxirreduçãoRESUMO
BACKGROUND: Dialysis practice has a particularly high environmental impact, including responsible for carbon emissions and climate change. Insufficient research has been conducted on environmental sustainability activities in dialysis therapy in Japan. METHODS: We conducted an online Green Survey comprising 30 question items based on a previously conducted survey in Australia. Between August and September 2023, this was sent to members of the Japanese Association of Dialysis Physicians, including hospital and clinic physicians, working across 885 dialysis facilities in Japan. RESULTS: In total, 255 (29%) facilities responded to the survey. More than half of the facilities (n = 157; 61.6%) responded that they did not have a strategy, policy, or action plan for environmental sustainability. In four-fifths of the facilities (n = 208; 81.6%), no "green team" or committee had been formed to promote environmental protection. By contrast, most of the surveyed facilities had emergency strategies for natural disasters, such as covering for patient visits and staff commuting during extreme weather conditions (n = 169; 66.3%), water shortages (n = 159; 62.4%), and power outages (n = 188; 73.7%). CONCLUSIONS: Following the UK, Australia and New Zealand, and Portugal, this is the fourth Green Survey to be conducted, and the first on environmental sustainability among kidney health-care providers in Japan. The results indicated that daily activities for environmental protection are still lacking at many facilities, even though the management of dialysis treatment during a natural disaster is well conducted.
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Diálise Renal , Japão , Humanos , Conservação dos Recursos Naturais , Inquéritos e Questionários , Instituições de Assistência Ambulatorial , Mudança Climática , População do Leste AsiáticoRESUMO
BACKGROUND: Upward-directed exit-site has been believed to be the worst for frequent ESI by an old retrospective study using straight catheters. No comparison study of 3 exit-site directions using swan-neck catheter has been performed regarding which direction is the best for our endpoints, Easy-to-see the backside area of exit-site: ESBE, Easy-to-disinfect the backside area of exit-site: EDBE, reduction of both exit-site infection (ESI), symptomatic catheter dislocation and peritonitis. METHODS: We assessed the relationship of exit-site direction with our endpoints in a quantitative cross-sectional, multicentered questionnaire survey. Patients who received either non-surgical catheter implantation or exit-site surgery were excluded. RESULTS: The numbers (percentage) of exit-site directions in included 291 patients were upward 79 (26.0), lateralward 108 (37.5) and downward 105 (36.5). Cochran-Armitage analysis showed a significant step-ladder increase in the prevalence of ESI as the direction changed from upward to lateralward to downward (0.15 ± 0.41, 0.25 ± 0.54, 0.38 ± 0.69 episodes/patient-year, p = 0.03). Multivariable regression analysis revealed the upward exit-site independently associates with both higher frequency of ESBE (OR 5.55, 95% CI 2.23-16.45, p < 0.01) and reduction of prevalence of ESI (OR 0.55, 95%CI 0.27-0.98, p = 0.04). Positive association between the prevalence of symptomatic catheter dislocation and ESI (OR 2.84, 95% CI 1.27-7.82, p = 0.01), and inverse association between EDBE and either prevalence of symptomatic catheter dislocation (OR 0.27, 95% CI 0.11-0.72) or peritonitis (OR 0.48, 95% CI 0.23-0.99) observed. CONCLUSION: Upward-directed swan-neck catheter exit-site may be the best for both ESBE and prevention of ESI. EDBE may reduce catheter dislocation and peritonitis. Symptomatic catheter dislocation may predict ESI.
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Infecções Relacionadas a Cateter , Cateteres de Demora , Diálise Peritoneal , Peritonite , Humanos , Masculino , Feminino , Estudos Transversais , Pessoa de Meia-Idade , Cateteres de Demora/efeitos adversos , Idoso , Infecções Relacionadas a Cateter/prevenção & controle , Infecções Relacionadas a Cateter/epidemiologia , Infecções Relacionadas a Cateter/etiologia , Peritonite/prevenção & controle , Peritonite/etiologia , Peritonite/epidemiologia , Diálise Peritoneal/instrumentação , Diálise Peritoneal/efeitos adversos , Inquéritos e Questionários , Fatores de RiscoRESUMO
ABSTRACT: Acute leukemia cells require bone marrow microenvironments, known as niches, which provide leukemic cells with niche factors that are essential for leukemic cell survival and/or proliferation. However, it remains unclear how the dynamics of the leukemic cell-niche interaction are regulated. Using a genome-wide CRISPR screen, we discovered that canonical BRG1/BRM-associated factor (cBAF), a variant of the switch/sucrose nonfermenting chromatin remodeling complex, regulates the migratory response of human T-cell acute lymphoblastic leukemia (T-ALL) cells to a niche factor CXCL12. Mechanistically, cBAF maintains chromatin accessibility and allows RUNX1 to bind to CXCR4 enhancer regions. cBAF inhibition evicts RUNX1 from the genome, resulting in CXCR4 downregulation and impaired migration activity. In addition, cBAF maintains chromatin accessibility preferentially at RUNX1 binding sites, ensuring RUNX1 binding at these sites, and is required for expression of RUNX1-regulated genes, such as CDK6; therefore, cBAF inhibition negatively impacts cell proliferation and profoundly induces apoptosis. This anticancer effect was also confirmed using T-ALL xenograft models, suggesting cBAF as a promising therapeutic target. Thus, we provide novel evidence that cBAF regulates the RUNX1-driven leukemic program and governs migration activity toward CXCL12 and cell-autonomous growth in human T-ALL.
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Subunidade alfa 2 de Fator de Ligação ao Core , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Humanos , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Medula Óssea/metabolismo , Cromatina , Linfócitos T/metabolismo , Linhagem Celular Tumoral , Microambiente TumoralRESUMO
Trauma has been suspected as a factor leading to development of angiosarcoma, a malignant soft-tissue tumor. We conducted a forensic autopsy to investigate a putative relation between a motor vehicle collision and the driver's later death from angiosarcoma. A vehicle operated by a man in his 60 s collided with an oncoming vehicle at a curve. The victim noticed no injury at the scene. However, 45 days later, he was transferred to an emergency room with dyspnea and bloody sputum. After diagnosis of angiosarcoma, he died of respiratory failure 132 days later. The bereaved family speculated about a relation between the collision and angiosarcoma onset. At autopsy, tumor cells of the scalp had metastasized to the lung, pleura, liver, and spleen. Histopathological examinations revealed characteristic features of angiosarcoma with positive immune-staining for CD31, CD34, and factor VIII. When a person dies some time after a collision, it is designated as a delayed death. In such cases, the relevance of trauma to the person's death is often an issue of concern. Because the interval between trauma and angiosarcoma development was short, only 45 days, the angiosarcoma might be coincidental. Therefore, we rejected the relation. Forensic experts sometimes need to investigate such inquiries.
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Hemangiossarcoma , Masculino , Humanos , Hemangiossarcoma/diagnóstico , Pulmão/patologia , Veículos AutomotoresRESUMO
BACKGROUND: This multi-institutional, observational study examined whether the outcomes after peritoneal dialysis (PD) catheter placement in Japan meet the audit criteria of the International Society for Peritoneal Dialysis (ISPD) guideline and identified factors affecting technique survival and perioperative complications. METHODS: Adult patients who underwent first PD catheter placement for end-stage kidney disease between April 2019 and March 2021 were followed until PD withdrawal, kidney transplantation, transfer to other facilities, death, 1 year after PD start or March 2022, whichever came first. Primary outcomes were time to catheter patency failure and technique failure, and perioperative infectious complications within 30 days of catheter placement. Secondary outcomes were perioperative complications. Appropriate statistical analyses were performed to identify factors associated with the outcomes of interest. RESULTS: Of the total 409 patients, 8 who underwent the embedded catheter technique did not have externalised catheters. Of the 401 remaining patients, catheter patency failure occurred in 25 (6.2%). Technical failure at 12 months after PD catheter placement calculated from cumulative incidence function was 15.3%. On Cox proportional hazards model analysis, serum albumin (hazard ratio (HR) 0.44; 95% confidence interval (CI) 0.27-0.70) and straight type catheter (HR 2.14; 95% CI 1.24-3.69) were the independent risk factors for technique failure. On logistic regression analysis, diabetes mellitus was the only independent risk factor for perioperative infectious complications (odds ratio 2.70, 95% CI 1.30-5.58). The occurrence rate of perioperative complications generally met the audit criteria of the ISPD guidelines. CONCLUSION: PD catheter placement in Japan was proven to be safe and appropriate.
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Falência Renal Crônica , Diálise Peritoneal , Adulto , Humanos , Diálise Peritoneal/efeitos adversos , Diálise Peritoneal/métodos , Cateteres de Demora/efeitos adversos , Japão , Cateterismo/métodos , Peritônio , Falência Renal Crônica/terapia , Falência Renal Crônica/etiologiaRESUMO
Drosophila courtship studies have elucidated several principles of the neurogenetic organization of complex behaviour. Through an integration across sensory modalities, males perform stereotypic patterns of chasing, courtship song production and copulation attempts. Here we report a serendipitous finding that intense light not only enhances courtship toward female targets but also triggers unexpected courtship behaviours among male flies. Strikingly, in wild-type male-only chambers, we observed extreme behavioural manifestations, such as 'chaining' and 'wheeling', resembling previously reported male-male courtship behaviours in fruitless mutants and in transformants with ectopic mini-white+ overexpression. This male-male courtship was greatly diminished in a variety of visual system mutants, including disrupted phototransduction (norpA), eliminated eye-colour screening pigments (white), or deletion of the R7 photoreceptor cells (sevenless). However, light-induced courtship was unhampered in wing-cut flies, despite their inability to produce courtship song, a major acoustic signal during courtship. Unexpectedly the olfactory mutants orco and sbl displayed unrestrained male-male courtship. Particularly, orco males attained maximum courtship scores under either dim or intense light conditions. Together, our observations support the notion that the innate male courtship behaviour is restrained by olfactory cues under normal conditions but can be unleashed by strong visual stimulation in Drosophila.
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Proteínas de Drosophila , Drosophila , Animais , Masculino , Feminino , Drosophila melanogaster/genética , Corte , Comportamento Sexual Animal/fisiologia , Proteínas de Drosophila/genéticaRESUMO
BACKGROUND: Cardiac hypertrophy, which develops in middle-aged and older individuals as a consequence of hypertension and obesity, is an established risk factor for sudden cardiac death (SCD). However, it is sometimes difficult to differentiate SCD with acquired cardiac hypertrophy (SCH) from compensated cardiac hypertrophy (CCH), at autopsy. We aimed to elucidate the proteomic alteration in SCH, which can be a guideline for future postmortem diagnosis. METHODS: Cardiac tissues were sampled at autopsy. SCH group consisted of ischemic heart failure, hypertensive heart failure, and aortic stenosis. CCH group included cases of non-cardiac death with cardiac hypertrophy. The control group comprised cases of non-cardiac death without cardiac hypertrophy. All patients were aged > 40 years, and hypertrophic cardiomyopathy was not included in this study. We performed histological examination and shotgun proteomic analysis, followed by quantitative polymerase chain reaction analysis. RESULTS: Significant obesity and myocardial hypertrophy, and mild myocardial fibrosis were comparable in SCH and CCH cases compared to control cases. The proteomic profile of SCH cases was distinguishable from those of CCH and control cases, and many sarcomere proteins were increased in SCH cases. Especially, the protein and mRNA levels of MYH7 and MYL3 were significantly increased in SCH cases. CONCLUSION: This is the first report of cardiac proteomic analysis in SCH and CCH cases. The stepwise upregulation of sarcomere proteins may increase the risk for SCD in acquired cardiac hypertrophy before cardiac fibrosis progresses significantly. These findings can possibly aid in the postmortem diagnosis of SCH in middle-aged and older individuals.
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Cardiomiopatias , Insuficiência Cardíaca , Hipertensão , Pessoa de Meia-Idade , Humanos , Idoso , Proteômica , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/patologia , Fibrose , Hipertensão/complicações , Obesidade , CardiomegaliaRESUMO
Although exposure-directed busulfan (BU) dosing can improve allogeneic hematopoietic stem cell transplantation outcomes, there is still large variability in BU exposure with test dose alone due to changes in BU clearance caused by drug interactions. We conducted a single-arm phase II trial using the combined test dose and therapeutic drug monitoring strategy (PK-guided group) and compared the outcomes with an external historical cohort receiving a fixed-dose (fixed-dose group). The first eight and second eight doses were adjusted based on the area under the blood concentration-time curve (AUC) of the test and first doses, respectively, targeting a total AUC of 82.1 mg·h/L. All patients received either BU and cyclophosphamide conditioning (BU/CY) or fludarabine (FLU)-containing conditioning. The BU clearance at the first dose decreased more in patients receiving FLU than in those receiving BU/CY; however, BU clearance also declined over time in patients who received BU/CY. The simulated total AUC (sAUC) with test dose only was significantly higher in patients who received FLU than in those who received BU/CY, but sAUC with the combined strategy was comparable. The 100-day progression-free survival was 85.5% (95% confidence interval [CI]: 71.9-92.8%), and was not inferior to that in the fixed-dose group. For the FLU-containing regimens, the PK-guided group showed decreased relapse (0.0% vs. 26.9%, p = 0.03), and favorable overall survival (75.1% vs. 57.0%, p = 0.07) at 1 year. The combined strategy effectively controlled the BU exposure close to the target levels, potentially improving efficacy, especially in patients receiving the FLU-containing regimen. Clinical evaluation of efficacy of dose-modified intravenous busulfan in allogeneic hematopoietic stem cell transplantation for hematological malignancy (#UMIN000014077, June 15th, 2014).
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Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Humanos , Bussulfano , Ciclofosfamida , Monitoramento de Medicamentos , Neoplasias Hematológicas/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Condicionamento Pré-Transplante , VidarabinaRESUMO
Concomitant with nephrotic syndrome and multicentric castleman's disease (MCD) has only been described in a limited number of small studies and case reports. Among those, none confirmed the renal pathology prior to the onset of MCD, and none of the cases had a history of nephrotic syndrome. A 76 year-old Japanese man visited a nephrologist because of incident nephrotic syndrome. He had previously experienced three episodes of nephrotic syndrome, the last one 13 years ago, and had been diagnosed with membranous nephropathy by renal biopsy. Apart from these previous episodes, he also suffered from systemic lymphadenopathy, anemia, elevated C-reactive protein, polyclonal hypergammopathy, and elevated interleukin (IL)-6. An inguinal lymph node biopsy revealed CD138-positive plasma cells in the interfollicular region. Based on these findings, MCD was diagnosed. Renal biopsy indicated primary membranous nephropathy with spike lesions and bubbling in the basement membranes and deposition of immunoglobulin (Ig) G, IgA, IgM, and phospholipase A2 receptor along the glomerular basement membrane. Corticosteroid monotherapy successfully reduced the edema, proteinuria, and IL-6, but hypoalbuminemia was not sufficiently improved due to castleman's disease and remission of the nephrotic syndrome was not achieved. Later, tocilizumab was administered for remission induction in another facility. To the best of our knowledge, this represents the first report of Castleman's disease with previously diagnosed membranous nephropathy. This case does not provide a causal mechanism for the pathophysiology, but it may be worth suggesting possible involvement of MCD as a trigger for recurrence of membranous nephropathy.
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Amphipathic peptides composed of cationic amino acids and hydrophobic amino acids have cell-penetrating ability and are often used as a delivery tool for membrane-impermeable compounds. Small interfering RNA (siRNAs) are one of the delivery targets for such cell-penetrating peptides (CPPs). Cationic CPPs can associate with anionic siRNAs by electrostatic interactions resulting in the formation of nano-sized complexes, which can deliver siRNAs intracellularly. CPPs containing unnatural amino acids offer promising tools to siRNA delivery. However, the detailed structure-activity relationship in siRNA delivery has been rarely studied. In the current study, we designed peptides containing dipropylglycine (Dpg) and explored the cellular uptake and cytotoxicity of peptide/siRNA complexes. The amphipathic structure of the peptides played a key role in complexation with siRNAs and intracellular siRNA delivery. In the amphipathic peptides, cellular uptake of siRNA increased with increasing peptide length, but cytotoxicity was reduced. A peptide containing four Dpg exhibited an effective gene-silencing effect with small amounts of peptides without cytotoxicity in medium containing serum. These findings will be helpful for the design of novel CPPs for siRNA delivery.
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Peptídeos Penetradores de Células , Valina , RNA Interferente Pequeno , AminoácidosRESUMO
The Marabou stork (Leptoptilos crumenifer) is a typical scavenging bird and adapted to the Savannah environment, where they show a carnivorous feeding style. However, Marabou stork recently penetrated into the city areas and acclimatized to the urban environment, where they modified their feeding habits to an omnivorous type toward more carbohydrate. To reveal their adaptation to the variable feeding customs, this study compared the gut microbiomes and chemical compositions of feces of Marabou storks inhabiting two different locations in peri urban Kampala: one is a slaughter house floc that predicted their original carnivorous feeding, and the other is a landfill floc that adapted more to the omnivorous feeding. 16S rRNA gene sequencing analysis revealed more diverse gut microbiome, more enriched Lactobacilli, and less abundant Peptostreptococci in the landfill flock comparing to the slaughter house flock. Isolation work and predicted metagenome analysis confirmed more diverse Lactobacilli and more enriched functions for carbohydrate metabolism in the landfill flock. In addition, chemical composition of feces revealed higher ammonia in the former, which is consisting with higher Peptostreptococci and their practice of carnivorous feeding. These results highlighted their adaptation to the variable feeding environment, which presumably protects their health and ensure survival of species.
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Aves , Microbiota , Animais , Uganda , RNA Ribossômico 16S/genética , Aclimatação , FezesRESUMO
Most combined peritoneal dialysis and hemodialysis therapies are used to compensate for the lack of dialysis volume and efficiency in pre-started peritoneal dialysis patients. The aim was to determine the effects on both peritoneal dialysis and residual renal function when proactively combined therapy is started at dialysis induction. This report was based on observation of 10 patients who initiated dialysis therapy with a combination of peritoneal and hemodialysis at induction, and the control group consisted of 24 patients with peritoneal monotherapy in a single dialysis center. The technical survival of peritoneal dialysis therapy and urinary volume and creatinine clearance as residual renal function were assessed. Technical survival of peritoneal dialysis during the 5-year observation period was much better in patients who started with proactive combination therapy than with peritoneal dialysis monotherapy. Between induction and 24 months later, median urinary volume (interquartile value) changed from 1500 (1100-1583) to 800 (545-1875) mL/day and from 1600 (1300-2150) to 1480 (115-1885) mL/day for peritoneal alone and for combination therapy, respectively. Creatinine clearance values changed from 7.0 (6.0-8.7) to 2.0 (1.0-3.0) mL/min for peritoneal alone and from 6.0 (4.0-7.3) to 3.0 (0.5-4.0) mL/min for combination therapy. Though some possible confounding factors, including selection bias, cannot be ruled out, this investigation suggests the benefit of proactive combination dialysis therapy on the sustainability of peritoneal dialysis and residual renal function.
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Falência Renal Crônica , Diálise Peritoneal , Humanos , Creatinina , Diálise Renal , Peritônio , Rim/fisiologia , Falência Renal Crônica/terapiaRESUMO
Homicide by electrocution is rare in forensics, and the identification of the cause of death can be quite difficult when the electric device is removed from the scene. We present an instance where the police were unsure of homicide in the initial investigation. The offender used hand-made electrode plates for electrocution, which produced unique electric marks different from those produced by common electric devices such as electric wires. To the best of our knowledge, this is the first report of homicide by electrocution with electrode plates. We believe that the macroscopic and microscopic findings in this instance are quite valuable for forensic practitioners.
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Malignant pleural mesothelioma is rarely associated with nephrotic syndrome. Cryoglobulinemia is found in various pathological statuses, such as hepatitis C virus infection but rarely in malignant neoplasms. We recently encountered a patient with malignant mesothelioma coincident with nephrotic syndrome and cryoglobulinemia in the course of chemotherapy. A 60-year-old man employed as a building painter was diagnosed with malignant mesothelioma by lung biopsy two years earlier and was started on chemotherapy. Nivolumab seemed effective in controlling mesothelioma, but skin immune-related adverse events occurred during the course of treatment. After discontinuation of nivolumab and administration of gemcitabine as an alternative therapy, the patient was referred to a nephrologist because of the subsequent development of edema, renal injury, and proteinuria. Following the investigation, he was diagnosed with nephrotic syndrome and cryoglobulinemia with C4-dominant cold activation. However, a percutaneous renal biopsy could not be performed due to persistent severe cough induced by pleural involvement. The patient died a little over three years after the pathological diagnosis of pleural mesothelioma. Our case had three key features nephrotic syndrome was possibly associated with malignant mesothelioma; cryoglobulinemia occurred in malignant mesothelioma; and concomitant nephrotic syndrome and cryoglobulinemia occurred after chemotherapy. Unfortunately, our rare case lacks a basis in renal pathology or evidence of links between the pathogenesis of malignant mesothelioma, cryoglobulinemia, and nephrotic syndrome. This case does not provide a causal mechanism, but may be worth adding to the case list as one of the rare renal involvement in a patient with malignant mesothelioma.