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Radiation exposure in a therapeutic setting or during a mass casualty event requires improved medical triaging, where the time to delivery and quantity of medical countermeasures are critical to survival. Radiation-induced liver injury (RILI) and fibrosis can lead to death, but clinical symptoms manifest late in disease pathogenesis and there is no simple diagnostic test to determine RILI. Because animal models do not completely recapitulate clinical symptoms, we used a human liver-on-a-chip model to identify biomarkers of RILI. The goals of this study were: 1. to establish a microfluidic liver-on-a-chip device as a physiologically relevant model for studying radiation-induced tissue damage; and 2. to determine acute changes in RNA expression and biological pathway regulation that identify potential biomarkers and mechanisms of RILI. To model functional human liver tissue, we used the Emulate organ-on-a-chip system to establish a co-culture of human liver sinusoidal endothelial cells (LSECs) and hepatocytes. The chips were subject to 0 Gy (sham), 1 Gy, 4 Gy, or 10 Gy irradiation and cells were collected at 6 h, 24 h, or 7 days postirradiation for RNA isolation. To identify significant expression changes in messenger RNA (mRNA) and long non-coding RNA (lncRNA), we performed RNA sequencing (RNASeq) to conduct whole transcriptome analysis. We found distinct differences in expression patterns by time, dose, and cell type, with higher doses of radiation resulting in the most pronounced expression changes, as anticipated. Ingenuity Pathway Analysis indicated significant inhibition of the cell viability pathway 24 h after 10 Gy exposure in LSECs but activation of this pathway in hepatocytes, highlighting differences between cell types despite receiving the same radiation dose. Overall, hepatocytes showed fewer gene expression changes in response to radiation, with only 3 statistically significant differentially expressed genes at 7 days: APOBEC3H, PTCHD4, and GDNF. We further highlight lncRNA of interest including DINO and PURPL in hepatocytes and TMPO-AS1 and PRC-AS1 in LSECs, identifying potential biomarkers of RILI. We demonstrated the potential utility of a human liver-on-a-chip model with primary cells to model organ-specific radiation injury, establishing a model for radiation medical countermeasure development and further biomarker validation. Furthermore, we identified biomarkers that differentiate radiation dose and defined cell-specific targets for potential radiation mitigation therapies.
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BACKGROUND/AIM: Sorafenib and lenvatinib have long been used as a first-line treatment for advanced hepatocellular carcinoma (HCC). Along with the development of systemic chemotherapy for HCC, the concept of conversion hepatectomy has recently become widespread. The present study aimed to assess the clinical outcomes of sorafenib and lenvatinib for HCC regarding the possibility of conversion hepatectomy in clinical practice. PATIENTS AND METHODS: A total of 295 patients with advanced HCC receiving sorafenib and lenvatinib, accounting for 306 treatments (sorafenib, n=157; lenvatinib, n=149, 11 patients received lenvatinib after sorafenib treatment) at five different institutions were enrolled. Patients were assessed for their clinical characteristics and therapeutic response using both Response Evaluation Criteria in Solid Tumors criteria (RECIST) and modified RECIST (mRECIST) criteria. Additionally, an indication of surgery after tyrosine kinase inhibitor administration was determined based on the tumor status of patients. RESULTS: The median survival times of patients treated with sorafenib and lenvatinib were 12.8 and 16.4 months, respectively, without significant difference (p=0.1645). The objective response rates (ORR) of sorafenib based on mRECIST and RECIST were 10.1% and 5.9%, respectively, and those of lenvatinib were 38.1% and 19.0%, respectively. Among the 306 treatments, two cases (sorafenib and lenvatinib, one each) underwent hepatectomy after systemic chemotherapy. CONCLUSION: Few cases with unresectable HCC were amenable to conversion hepatectomy after sorafenib and lenvatinib treatments due to the limited ORR by RECIST. Cautious approach must be taken when administering neoadjuvant chemotherapy aimed at conversion hepatectomy.
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Carcinoma Hepatocelular , Hepatectomía , Neoplasias Hepáticas , Compuestos de Fenilurea , Quinolinas , Sorafenib , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/mortalidad , Quinolinas/uso terapéutico , Quinolinas/administración & dosificación , Compuestos de Fenilurea/uso terapéutico , Sorafenib/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , Anciano de 80 o más Años , Resultado del Tratamiento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Antineoplásicos/uso terapéuticoRESUMEN
Dissipative structures often appear as an unstable counterpart of ordered structures owing to fluctuations that do not form a homogeneous phase. Even a multiphase mixture may simultaneously undergo one chemical reaction near equilibrium and another one that is far from equilibrium. Here, we observed in real time crystal seed formation and simultaneous nanocrystal aggregation proceeding from CeIV complexes to CeO2 nanoparticles in an acidic aqueous solution, and investigated the resultant hierarchical nanoarchitecture. The formed particles exhibited two very different size ranges, resulting in further pattern formation with opalescence. The hierarchically assembled structures in solutions were CeO2 colloids, viz. primary core clusters (1-3 nm) of crystalline ceria and secondary clusters (20-30 nm) assembled through surface ions. Such self-assembly is widespread in multi-component complex fluids, paradoxically moderating hierarchical reactions. Stability and instability are not only critical but also complementary for co-optimisation around the nearby free energy landscape prior to bifurcation.
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In this study, we determined effects of an anionic siRNA delivery vector, siRNA ternary complex, which is constructed with biodegradable dendrigraft poly-L-lysine (DGL) and γ-polyglutamic acid (γ-PGA) on the melanoma cells and melanoma lung metastasis. The siRNA ternary complex showed high cellular uptake and silencing effect in melanoma cell line B16-F10/Luc cells. After intravenous administration of the siRNA ternary complex, high silencing effect was also observed in the lung of B16-F10/Luc melanoma metastasis model mice. Therefore, we applied vascular endothelial growth factor (VEGF)-siRNA on the siRNA ternary complex and determined the effect on the melanoma lung metastasis. The siRNA ternary complex containing VEGF-siRNA reduced VEGF protein levels significantly in in vitro and in vivo, and the complex successfully inhibited melanoma lung metastasis. This biodegradable and effective siRNA delivery vector, siRNA ternary complex, could be available for clinical trials.
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Neoplasias Pulmonares , Melanoma Experimental , Ácido Poliglutámico , Polilisina , ARN Interferente Pequeño , Factor A de Crecimiento Endotelial Vascular , ARN Interferente Pequeño/administración & dosificación , ARN Interferente Pequeño/farmacología , Animales , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/patología , Ratones , Melanoma Experimental/patología , Ácido Poliglutámico/química , Ácido Poliglutámico/análogos & derivados , Línea Celular Tumoral , Factor A de Crecimiento Endotelial Vascular/genética , Polilisina/química , Ratones Endogámicos C57BL , Silenciador del Gen , Melanoma/patología , Melanoma/genéticaRESUMEN
Cellular traction forces are contractile forces that depend on the material/substrate stiffness and play essential roles in sensing mechanical environments and regulating cell morphology and function. Traction forces are primarily generated by the actin cytoskeleton and transmitted to the substrate through focal adhesions. The cell nucleus is also believed to be involved in the regulation of this type of force; however, the role of the nucleus in cellular traction forces remains unclear. In this study, we explored the effects of nucleus-actin filament coupling on cellular traction forces in human dermal fibroblasts cultured on substrates with varying stiffness (5, 15, and 48 kPa). To investigate these effects, we transfected the cells with a dominant-negative Klarsicht/ANC-1/Syne homology (DN-KASH) protein that was designed to displace endogenous linker proteins and disrupt nucleus-actin cytoskeleton connections. The force that exists between the cytoskeleton and the nucleus (nuclear tension) was also evaluated with a fluorescence resonance energy transfer (FRET)-based tension sensor. We observed a biphasic change in cellular traction forces with a peak at 15 kPa, regardless of DN-KASH expression, that was inversely correlated with the nuclear tension. In addition, the relative magnitude and distribution of traction forces in nontreated wild-type cells were similar across different stiffness conditions, while DN-KASH-transfected cells exhibited a different distribution pattern that was impacted by the substrate stiffness. These results suggest that the nucleus-actin filament coupling play a homeostatic role by maintaining the relative magnitude of cellular traction forces in fibroblasts under different stiffness conditions.
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This study experimentally investigated acoustically driven gas-mixture separation. Acoustic wave propagation in a narrow tube can induce gas-mixture separation. A binary mixture of helium and argon was used as the gas mixture. The pressure amplitude of the acoustic wave and initial molar fraction of the helium gas were investigated. The obtained experimental data indicated that the molar fraction initially increased with increasing pressure amplitude, whereas the saturated molar fraction did not show a clear dependence on the pressure. Although the degree of separation was smaller with purer helium, gas-mixture separation occurred under all conditions within the experimental range.
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BACKGROUND: Lacosamide (LCM) has become commonly used for focal onset seizures due to its high tolerability and low drug interactions. Unlike patients on hemodialysis (HD), pharmacokinetic data and dosing recommendations for patients undergoing peritoneal dialysis (PD) are scant. CASE REPORT: A 2-year-old girl with end-stage kidney disease undergoing PD suffered prolonged focal onset seizures. The patient had congenital anomalies of the kidney and urinary tract associated with branchio-oto-renal syndrome due to an EYA1 gene mutation. She also had neurological sequelae from post-resuscitation encephalopathy at the age of one month. Antiseizure medication with few drug interactions, less impact on the neurodevelopmental state and possibility of intravenous administration was preferred. LCM met those criteria and was carefully administered. Although the patient had recurrent prolonged seizures during the titration periods, LCM could be continued without any apparent side effects. The blood levels of LCM increased linearly to the optimal level. We confirmed excretion of LCM in the PD fluid. Kidney transplantation was done three months after and her seizures were well controlled. CONCLUSIONS: LCM might be a promising option for patients undergoing PD. Due to the lower removal efficacy in PD compared with in HD, close attention should be paid to possible drug excess.
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Epilepsias Parciales , Epilepsia Generalizada , Diálisis Peritoneal , Insuficiencia Renal , Humanos , Niño , Femenino , Preescolar , Lacosamida/uso terapéutico , Anticonvulsivantes , Acetamidas/efectos adversos , Resultado del Tratamiento , Epilepsias Parciales/tratamiento farmacológico , Convulsiones/tratamiento farmacológico , Insuficiencia Renal/inducido químicamente , Insuficiencia Renal/tratamiento farmacológicoRESUMEN
OBJECTIVE: Transcutaneous auricular vagus nerve stimulation (taVNS) was performed in two patients suffering structural focal epilepsy with preserved intellectual ability to show the feasibility of taVNS for specific patient groups. CASE PRESENTATIONS: Patient 1 was a 24-year-old woman with frontal lobe epilepsy who had weekly hyperkinetic seizures despite multiple anti-seizure medications. Patient 2 was a 27-year-old woman with parietal lobe epilepsy and focal cortical dysplasia in the vicinity of the lipoma in the corpus callosum. She experienced weekly focal-impaired awareness seizures even with anti-seizure medication. taVNS was applied to the left earlobe of both patients at 1.5 mA, 25 Hz, 250 µs pulse width, and 30 s stimulation with 30 s rest for 4 h per day. Over an 8-week baseline and 20 weeks of stimulation, the rate of reduction in seizure frequency was evaluated, along with quality-of-life using the Short-Form 36-Item Health survey. RESULTS: At baseline, we measured up to 11 and 12 focal seizures per week in Patient 1 and 2, respectively, with both patients achieving seizure freedom after 4 and 20 weeks taVNS, respectively. Patient 1 and 2 were observed for 18 and 14 months, respectively, including the clinical trial and follow-up observation period. Quality-of-life ratings increased in both patients, and no significant adverse events occurred during the study period. During the maintenance period after 20 weeks, seizures remained absent in Patient 1, and seizures remained reduced in Patient 2. CONCLUSION: Our results demonstrate that taVNS may be a promising tool for structural focal epilepsy with preserved cognitive function. A multicenter double-blind clinical trial is needed to confirm the role of taVNS as an anti-seizure tool.
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Epilepsia del Lóbulo Frontal , Estimulación Eléctrica Transcutánea del Nervio , Estimulación del Nervio Vago , Adulto , Femenino , Humanos , Adulto Joven , Convulsiones/terapia , Convulsiones/etiología , Estimulación Eléctrica Transcutánea del Nervio/métodos , Nervio Vago/fisiología , Estimulación del Nervio Vago/métodosRESUMEN
BACKGROUND: Most long-term affected spinal muscular atrophy (SMA) type 1 patients have severe impairment of motor function and are dependent on mechanical ventilation with tracheostomy. The efficacy and safety of nusinersen in these patients have not been established. METHODS: We retrospectively evaluated the efficacy of intrathecal nusinersen treatment in patients with SMA type 1 who continued treatment for at least 12 months. There were three patients enrolled in our study (3, 4 and 16 years of age) who had severe impairment of gross motor function without head control or the ability to roll over. All three needed mechanical ventilation with tracheostomy and tube feeding. Motor function was assessed using the Children s Hospital of Philadelphia infant test of neuromuscular disorders (CHOP-INTEND) and the caregivers' evaluations. Concurrently, we examined nerve conduction longitudinally and compared compound motor action potential (CMAP) amplitudes. RESULTS: All patients continued nusinersen administration without significant adverse events for more than three years. While CHOP-INTEND scores did not remarkably increase, according to the caregivers, all three patients had improved finger or facial muscle movements that enabled them to make their intentions understood. Some CMAPs before treatment were not identified but became traces after nusinersen administration. CONCLUSIONS: The improvement in motor function that leads to smoother communication could be a basis for continuing nusinersen treatment. Currently available motor function scorings are not efficient for assessing therapeutic interventions in SMA patients with medical care complexity. Longitudinal nerve conduction studies could be an objective indicator.
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Atrofia Muscular Espinal , Atrofias Musculares Espinales de la Infancia , Niño , Lactante , Humanos , Estudios Retrospectivos , Potenciales de Acción , Atrofias Musculares Espinales de la Infancia/tratamiento farmacológico , Oligonucleótidos/uso terapéutico , Atrofia Muscular Espinal/tratamiento farmacológicoRESUMEN
Introduction: Dravet syndrome (DS) is an intractable epilepsy syndrome concomitant with neurodevelopmental disorder that begins in infancy. DS is dominantly caused by mutations in the SCN1A gene, which encodes the α subunit of a voltage-gated Na channel. Pre-synaptic inhibitory dysfunction is regarded as the pathophysiological mechanism, but an effective strategy for ameliorating seizures and behavioral problems is still under development. Here, we evaluated the effects of KRM-II-81, a newly developed positive allosteric modulator for α 2/3 subunit containing GABAA receptors (α2/3-GABAAR) in a mice model of DS both in vivo and at the neuronal level. Methods: We used knock-in mice carrying a heterozygous, clinically relevant SCN1A mutation (background strain: C57BL/6 J) as a model of the DS (Scn1a WT/A1783V mice), knock-in mouse strain carrying a heterozygous, clinically relevant SCN1A mutation (A1783V). Seizure threshold and locomotor activity was evaluated by using the hyperthermia-induced seizure paradigm and open filed test, respectively. Anxiety-like behavior was assessed by avoidance of the center region in locomotor activity. We estimated a sedative effect by the total distance traveled in locomotor activity and grip strength. Inhibitory post synaptic currents (IPSCs) were recorded from a hippocampal CA1 pyramidal neuron in an acutely prepared brain slice. Results: KRM-II-81 significantly increased the seizure threshold of Scn1a WT/A1783V mice in a dose-dependent manner. A low dose of KRM-II-81 specifically improved anxiety-like behavior of Scn1a WT/A1783V mice. A sedative effect was induced by relatively high dose of KRM-II-81 in Scn1a WT/A1783V mice, the dose of which was not sedative for WT mice. KRM-II-81 potentiated IPSCs by increasing its decay time kinetics. This effect was more prominent in Scn1a WT/A1783V mice. Discussion: Higher activation of α2/3-GABAAR by KRM-II-81 suggests a compensatory modification of post synaptic inhibitory function against presynaptic inhibitory dysfunction in Scn1a WT/A1783V. The increased sensitivity for KRM-II-81 may be relevant to the distinct dose-dependent effect in each paradigm of Scn1a WT/A1783V mice. Conclusion: Selective activation for α2/3-GABAAR by KRM-II-81 could be potential therapeutic strategy for treating seizures and behavioral problems in DS.
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Understanding clay flotation mechanisms has become a major concern because of the increasing level of environmental contamination of soil and ground water by heavy metals and radionuclides. Clays are often used as sorbents for extracting metals in indirect flotation processes but can function simultaneously as defoamers. However, how foam generation and stability depend on the molecular interactions between the clays and surfactant is still controversial. In the present study, an amine polyethoxylated surfactant was used as a bifunctional surfactant that collected clay particles and acted as a foaming agent in the flotation process. The pH conditions strongly affected the surfactant physicochemical properties, allowing the clay extraction efficiency to be tuned. The interfacial recovery factor of the clays almost reached 100% under acidic (pH < 6) and neutral (pH 6-10) conditions, whereas it was negative under alkaline conditions (pH > 10), contrary to expectations. To elucidate the mechanisms involved in the particle flotation process for each of the pH conditions, the bulk and foam phases were analyzed. The effects of electrostatic interactions between the solutes and multiscale structure on the clay extraction behavior were investigated by electrophoretic measurements, dynamic light scattering, small-angle neutron scattering, and image analysis. Based on these results, three flotation processes were found depending on pH range: surfactant foam fractionation at pH > 10; clay particle foam flotation at pH 6-10; and particle froth flotation at pH < 6.
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Radiation-related normal tissue injury sustained during cancer radiotherapy or in a radiological or mass casualty nuclear incident is a major health concern. Reducing the risk and mitigating consequences of radiation injury could have a broad impact on cancer patients and citizens. Efforts to discover biomarkers that can determine radiation dose, predict tissue damage, and aid medical triage are underway. Exposure to ionizing radiation causes changes in gene, protein, and metabolite expression that needs to be understood to provide a holistic picture for treating acute and chronic radiation-induced toxicities. We present evidence that both RNA (mRNA, microRNA, long noncoding RNA) and metabolomic assays may provide useful biomarkers of radiation injury. RNA markers may provide information on early pathway alterations after radiation injury that can predict damage and implicate downstream targets for mitigation. In contrast, metabolomics is impacted by changes in epigenetics, genetics, and proteomics and can be considered a downstream marker that incorporates all these changes to provide an assessment of what is currently happening within an organ. We highlight research from the past 10 years to understand how biomarkers may be used to improve personalized medicine in cancer therapy and medical decision-making in mass casualty scenarios.
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MicroARNs , Neoplasias , Traumatismos por Radiación , Humanos , Traumatismos por Radiación/etiología , Traumatismos por Radiación/genética , MicroARNs/genética , Biomarcadores , Epigénesis Genética , Neoplasias/genética , Neoplasias/radioterapia , RadiometríaRESUMEN
Objective: Loneliness is an important health problem in rural areas of Japan because of its ageing and declining population. Therefore, we investigated the association between loneliness and health. Materials and Methods: Self-administered questionnaires were distributed to rural adult residents. The Japanese 3-item versions of the UCLA Loneliness Scale, self-rated health (SRH), and objective health status (whether the respondents had a physical and/or mental illness) were used. We defined a UCLA score of four points or more as loneliness, an SRH of four points or more as a subjective healthy state, and no physical or mental illness as an objective healthy state. The association was adjusted for sociodemographic data, lifestyle habits, and isolation risk using logistic regression analysis. Results: The five-year population decline rate in the target areas was 10.2 to 12.3%. Of the 2,700 participants, there were 1,211 male and 1,489 female respondents, with an average age of 65.4 years. Moreover, 358 (13.6%) were living alone, and 829 (31.5%) were living in couple-only households. Among the participants, 1,395 (53.2%) experienced loneliness, 1,751 (65.7%) had good self-rated health, and 1,587 (60.8%) had objective health status. Loneliness was negatively associated with good SRH (OR=0.56, CI=0.45-0.70) and objective health status (OR=0.57, CI=0.46-0.71) after adjusting for sociodemographic data, lifestyle habits, and the risk of isolation. Statistically significant confounding factors for subjective and/or objective health status were employment, not smoking, obesity, exercise, having a family doctor, having an above-average number of teeth, and the ability to leave home. Conclusion: In an ageing and declining population, loneliness is an independent factor affecting the health status of rural residents and is not limited to older adults. Therefore, measures to reduce it are needed.
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OBJECTIVE: The efficacy of the mechanistic target of rapamycin inhibitor, sirolimus, was recently reported for patients more than 6 years of age by Kato et al. We evaluated the efficacy and safety of sirolimus in a 2-year-old patient with recurrent focal seizures with impaired consciousness after focal cortical dysplasia (FCD) type IIa resection. METHODS: The patient was a 2-year-old girl who had recurrent seizures after undergoing FCD resection at 4 months of age. The initial dose of sirolimus was 0.5 mg/day and was gradually increased using the trough blood concentration before oral administration as an index, and evaluation was performed at 92 weeks. RESULTS: The trough blood level of sirolimus was increased to 6.1 ng/mL and maintenance therapy was started at 40 weeks. Focal seizures with impairment of consciousness with tonic extension of the limbs decreased. No critically serious adverse events occurred. CONCLUSION: Sirolimus was effective against epileptic seizures from FCD type II even for a child under 5 years of age. There were no critically serious adverse events and administration could be continued.
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Epilepsia Generalizada , Epilepsia , Displasia Cortical Focal , Malformaciones del Desarrollo Cortical , Niño , Femenino , Humanos , Preescolar , Sirolimus/uso terapéutico , Sirolimus/farmacología , Convulsiones/tratamiento farmacológico , Convulsiones/etiología , Convulsiones/cirugía , Epilepsia/tratamiento farmacológico , Epilepsia/etiología , Epilepsia/cirugía , Malformaciones del Desarrollo Cortical/complicaciones , Malformaciones del Desarrollo Cortical/tratamiento farmacológico , Imagen por Resonancia MagnéticaRESUMEN
A 70s woman with advanced rectal cancer(AV 3 cm, type 2)was diagnosed as cT3N2M1a, Stage â £(UICC, TNM 8th) and underwent total neoadjuvant therapy(TNT)consisted of preoperative 5 Gy×5 short course RT followed by 5 courses of CAPOX plus BEV and CAPOX. Post-treatment endoscopy revealed nearCR, MRI failed to identify the primary tumor, and the mesenteric and lateral lymph node enlargement had disappeared. The patient underwent robot-assisted low anterior resection, bilateral lymph node dissection, and temporary ileal colostomy. Postoperative pathological findings were ypT0N0M0, Stage 0, and the efficacy evaluation was TRG 0(AJCC)with no residual tumor including lateral lymph nodes. The patient was discharged on the 16th day without any postoperative complications and is currently alive 6 months postoperatively without recurrence.
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Linfadenopatía , Neoplasias del Recto , Procedimientos Quirúrgicos Robotizados , Femenino , Humanos , Terapia Neoadyuvante , Ganglios Linfáticos/patología , Escisión del Ganglio Linfático , Neoplasias del Recto/cirugía , Estudios RetrospectivosRESUMEN
We report a case of 72s male with locally advanced sigmoid colon cancer. Colonoscopy revealed an advanced sigmoid colon cancer(AV 15 cm, type 2, semi-peripheral, deeper than T3). He was diagnosed as cT4bN2M0, cStage â ¢c(Japanese Classification of Colorectal, appendiceal, and, Carcinoma, 9th edition), and was given chemotherapy as preoperative treatment. He was treated with CAPOX plus BEV as neoadjuvant chemotherapy. Preoperative diagnosis was ycT4bN0M0, ycStage â ¡c. The robot assisted high anterior resection and partial bladder resection were performed. The bladder was sutured under robotic assistance. The residual bladder capacity was 100 mL. Postoperative diagnosis was ypT0N0M0, ypStage 0, TRG 0 (AJCC). We experienced a case of neoadjuvant chemotherapy for rectosigmoid colon cancer with bladder invasion, which resulted in pCR.
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Robótica , Neoplasias del Colon Sigmoide , Humanos , Masculino , Vejiga Urinaria/cirugía , Terapia Neoadyuvante , Neoplasias del Colon Sigmoide/cirugía , Fluorouracilo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
There is an ever-increasing body of evidence that metallic complexes involving amphiliphic ligands do not form normal solutions in organic solvents. Instead, they form complex fluids with intricate structures. For example, the metallic complexes may aggregate into clusters, and these clusters themselves may aggregate into superclusters. To gain a deeper insight into the mechanisms at play, we have used an improved force field to conduct extensive molecular dynamics simulations of a system composed of zirconium nitrate, water, nitric acid, tri-n-butyl phosphate, and n-octane. The important new finding is that a dynamic equilibrium between the cis and trans isomers of the metal complex is likely to play a key role in the aggregation behavior. The isolated cis and trans isomers have similar energies, but simulation indicates that the clusters consist predominantly of cis isomers. With increasing metal concentration, we hypothesize that more clustering occurs and the chemical equilibrium shifts toward the cis isomer. It is possible that such isomeric effects play a role in the liquid-liquid extraction of other species and the inclusion of such effects in flow sheet modeling may lead to a better description of the process.
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BACKGROUND: Hydrocephalus is one of the most common presentations of occipital encephaloceles and usually develops within the first year of life. This case report presents a rare case of late-onset obstructive hydrocephalus associated with occipital encephalocele with an extraordinarily large occipital skull defect. CASE REPORT: At birth, a newborn girl presented with an absence of a vast amount of occipital cranium and skin and was diagnosed with occipital hydroencephalomeningocele. Under meticulous sterile management, the affected area was successfully epithelialized, and the patient was discharged without infectious complication. Despite an obstructed cerebral aqueduct, she grew without any signs of hydrocephalus until the age of 7 years. Her gait gradually worsened, and imaging tests at the age of 8 years revealed markedly enlarged lateral and third ventricles but not the fourth ventricle. Endoscopic third ventriculostomy successfully relieved her symptoms with improvement of hydrocephalus. CONCLUSION: This is the first case of late-onset obstructive hydrocephalus associated with an occipital encephalocele characterized by large-scale cranial bony defects. Although further investigation is required to elucidate the mechanism of hydrocephalus, this rare phenomenon should be noted during neurological and radiological follow-up.
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Hidrocefalia , Tercer Ventrículo , Humanos , Femenino , Recién Nacido , Niño , Ventriculostomía/métodos , Encefalocele/cirugía , Hidrocefalia/cirugía , Acueducto del Mesencéfalo/cirugía , Tercer Ventrículo/cirugía , Cráneo/cirugíaRESUMEN
74-year-old woman was diagnosed with locally advanced unresectable transverse colon cancer. She started CAPOX therapy as first-line therapy after ileostomy. After second course, MSI-high was detected, so nivolumab plus ipilimumab combination therapy was started as second-line therapy. After 4 courses of combination therapy, she was judged to be in partial response and surgery was performed. Histopathological diagnosis of the surgical specimen showed complete response, and she is still alive without recurrence 15 months after surgery.