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1.
Small ; : e2403582, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39285814

RESUMO

New devices inspired by flying seeds, or more technically by fruits with dispersal units, could have a significant impact for environmental monitoring and aerial seeding. Among the various types of dispersal units (e.g., winged, gliding), parachuted or plumed units offer the lowest vertical descent speed (i.e., 0.3-0.7 m s-1), making them an appealing solution for wind-driven distribution over large areas. Here, a biodegradable and porous parachute flier based on cellulose acetate, inspired by a Tragopogon pratensis fruit is presented. A micrometric-thick pappus is 3D printed and integrated with a porous colorimetric indicator or a porous beak, with micrometric pores, fabricated through injection molding and leaching techniques. Thanks to the bioinspired design and the lightweight porous structure, the artificial Tragopogon mimics the aerodynamics and descent speed of the natural species. Its feasibility is demonstrated in aerial seeding by integrating the beak with a mustard seed (as a model), and in environmental monitoring by coupling it with colorimetric indicators for rain pH and nitrate levels in soils. The proposed flier represents a significant advancement as it is the first parachute-like biodegradable solution, seamlessly integrated into natural ecosystems, thus contributing to moving a step forward in artificial solutions with zero impact.

2.
Mol Pharm ; 21(5): 2590-2605, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38656981

RESUMO

We report a novel utilization of a pH modifier as a disproportionation retardant in a tablet formulation. The drug molecule of interest has significant bioavailability challenges that require solubility enhancement. In addition to limited salt/cocrystal options, disproportionation of the potential salt(s) was identified as a substantial risk. Using a combination of Raman spectroscopy with chemometrics and quantitative X-ray diffraction in specially designed stress testing, we investigated the disproportionation phenomena. The learnings and insight drawn from crystallography drove the selection of the maleate form as the target API. Inspired by the fumarate form's unique stability and solubility characteristics, we used fumaric acid as the microenvironmental pH modulator. Proof-of-concept experiments with high-risk (HCl) and moderate-risk (maleate) scenarios confirmed the synergistic advantage of fumaric acid, which interacts with the freebase released by disproportionation to form a more soluble species. The resultant hemifumarate helps maintain the solubility at an elevated level. This work demonstrates an innovative technique to mediate the solubility drop during the "parachute" phase of drug absorption using compendial excipients, and this approach can potentially serve as an effective risk-mitigating strategy for salt disproportionation.


Assuntos
Química Farmacêutica , Composição de Medicamentos , Fumaratos , Solubilidade , Fumaratos/química , Concentração de Íons de Hidrogênio , Composição de Medicamentos/métodos , Química Farmacêutica/métodos , Análise Espectral Raman/métodos , Difração de Raios X/métodos , Comprimidos/química , Sais/química , Maleatos/química , Excipientes/química , Disponibilidade Biológica
3.
Vascular ; : 17085381241273255, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39137929

RESUMO

INTRODUCTION: Chronic kidney disease (CKD) affects 13% of the global population and requires renal replacement therapy due to ESRD. Hemodialysis (HD) is the most common dialysis modality for ESRD patients, but establishing vascular access is challenging due to high morbidity and mortality rates. Arteriovenous fistulas (AVFs) are the gold standard for vascular access, but many fail due to anastomotic hemodynamics, vein diameter, and anastomatic suture technique. A prospective study was conducted to evaluate the impact of two continuous suturing techniques, the anchor technique and the parachute technique, on AVFs' initial outcomes. METHODS: This randomized, controlled study involved adult patients who presented for AVF creation at our center. We divided the patients into two groups: anchors and parachutes. Four skilled vascular access surgeons performed the procedures. The primary goal was functional maturation of the AVF, defined as an AVF fistula ready to be cannulated with a cannulating vein length of at least 10 cm, a diameter of more than 6 mm, a depth of less than 6 mm, and a flow rate of 600 mL/min. Secondary goals included patency and complications such as bleeding, infection, steal syndrome, and aneurysmal dilatation at the anastomosis site. AVFs were evaluated immediately after surgery and during follow-up visits at the outpatient clinic. A duplex scan was performed to measure flow at various intervals. All patients provided appropriate written consent. RESULT: The study involved 186 patients, with 86 excluded. 100 were randomized, with 5 cases losing follow-up and 3 deaths within 12 months. The follow-up continued until January 2024, with a mean of 8.6 months. The Parachute technique shows higher technical success (p value = 0.046) and primary patency at 30 days (p value = 0.014) compared to Anchor, but there is no statistical significance between both groups regarding functional maturation at 6 weeks (p value = 0.352). The parachute technique has a higher hematoma rate than the anchor technique (p value = 0.025), while other complications like intra-operative bleeding, postoperative bleeding, pseudoaneurysm formation, thrombosis, steal syndrome, and seroma formation show no significant differences. Nine patients, five of whom were diabetic and underwent conservative management, exhibited mild to moderate steal syndrome. This suggests an increased risk of steal syndrome among diabetic patients. CONCLUSION: The parachute technique for AVF creation offers better technical success and short-term primary patency outcomes, while both parachute and anchor techniques are equally effective for long-term functional maturation and overall complication rates.

4.
AAPS PharmSciTech ; 25(7): 210, 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39242368

RESUMO

Torsemide is a long acting pyridine sulfonylurea diuretic. Torsemide hydrochloride is widely used now, there are only a few organic acid salts reported. Cocrystallization with organic acids is an effective way to improve its solubility. Here, we reported maleate and phthalate of torsemide, in which the organic acid lost a proton transferring to the pyridine of torsemide, and torsemide interacted with organic acid through N+ - H⋯O- hydrogen bond to form salts crystal. Surprisingly, maleate showed a clear "spring" pattern in apparent solubility, whereas phthalate had a "spring-parachute" effect. Both crystalline salts kept a higher solubility than torsemide without falling. The "spring-parachute" effect of crystalline salts promoted rapid dissolution of torsemide and kept a high concentration, thereby increasing its bioavailability.


Assuntos
Cristalização , Sais , Solubilidade , Torasemida , Torasemida/química , Cristalização/métodos , Sais/química , Ligação de Hidrogênio , Diuréticos/química , Maleatos/química , Disponibilidade Biológica
5.
AAPS PharmSciTech ; 25(4): 84, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605282

RESUMO

The present work aims to explore the new solid forms of telmisartan (TEL) with alpha-ketoglutaric acid (KGA) and glutamic acid (GA) as potential coformers using mechanochemical approach and their role in augmentation in physicochemical parameters over pure crystalline TEL. Mechanochemical synthesis was performed using 1:1 stoichiometric ratio of TEL and the selected coformers in the presence of catalytic amount of ethanol for 1 h. The ground product was characterized by PXRD, DSC, and FTIR. The new solid forms were evaluated for apparent solubility, intrinsic dissolution, and physical stability. Preliminary characterization revealed the amorphization of the mechanochemical product as an alternate outcome of cocrystallization screening. Mechanistic understanding of the amorphous phase highlights the formation of amorphous-mediated cocrystallization that involves three steps, viz., molecular recognition, intermediate amorphous phase, and product nucleation. The solubility curves of both multicomponent amorphous solid forms (TEL-KGA and TEL-GA) showed the spring-parachute effect and revealed significant augmentation in apparent solubility (8-10-folds), and intrinsic dissolution release (6-9-folds) as compared to the pure drug. Besides, surface anisotropy and differential elemental distributions in intrinsic dissolution compacts of both solid forms were confirmed by FESEM and EDX mapping. Therefore, amorphous phases prepared from mechanochemical synthesis can serve as a potential solid form for the investigation of a cocrystal through amorphous-mediated cocrystallization. This has greater implications in solubility kinetics wherein the rapid precipitation of the amorphous phase can be prevented by the metastable cocrystal phase and contribute to the significant augmentation in the physicochemical parameters.


Assuntos
Telmisartan , Cristalização , Solubilidade , Estabilidade de Medicamentos
6.
Artigo em Zh | MEDLINE | ID: mdl-39075003

RESUMO

Objective: To investigate the relationship between ankle stability and associated muscle load around the ankle and the effect of a parachute ankle brace (PAB) on ankle inversion and associated muscle load around the ankle during landing through the simulated paratrooper semi-squat landing field experiment. Methods: In August 2021, 37 male paratroopers were randomly selected as the study objects to perform parachute landing training in the semi-squat posture on the 1.5 m and 2.0 m jump platforms with or without PAB, respectively. The coronal plane tilt angle of ankle joint and the percentage of maximum voluntary contraction (MVC%) of associated muscles around ankle joint during the process were measured and correlation analysis was conducted. And the effect of wearing PAB on the coronal plane tilt angle of ankle joint and the associated muscles around the ankle joint was analyzed. Results: During the semi-squat landing, the MVC% of the tibialis anterior muscle, lateral gastrocnemius muscle and peroneus longus muscle were positively correlated with the ankle coronal plane tilt angle in paratroopers wearing and without wearing PAB, and the correlations were statistically significant (P<0.05). At the same height, compared with those without PAB, the coronal plane tilt angle of the ankle joint decreased during semi-squat landing in paratroopers PAB, and the differences were statistically significant (P<0.05). At the landing moment of the same height, compared with those without PAB, the MVC% of lateral gastrocnemius muscle decreased and the MVC% of peroneus longus muscle increased in paratroopers wearing PAB, and the differences were statistically significant (P<0.05). After the landing moment until the standing stage (100-200 ms) at 1.5 m height, the MVC% of the tibialis anterior muscle decreased in paratroopers wearing PAB compared with those without PAB, and the differences were statistically significant (P<0.05). In the post-standing stage (200 ms) at 2.0 m height, the MVC% of the tibialis anterior muscle decreased in paratroopers wearing PAB compared with those without PAB, and the difference was statistically significant (P<0.05) . Conclusion: Wearing PAB can reduce the ankle coronal plane tilt angle, improve ankle stability, reduce the muscle load of the lateral gastrocnemius muscle at the moment of landing, and reduce the load of the tibialis anterior muscle after landing, but increase the peroneus longus muscle load at the moment of landing.


Assuntos
Articulação do Tornozelo , Músculo Esquelético , Humanos , Masculino , Articulação do Tornozelo/fisiologia , Músculo Esquelético/fisiologia , Adulto Jovem , Postura/fisiologia , Adulto , Braquetes , Fenômenos Biomecânicos , Suporte de Carga/fisiologia , Tornozelo/fisiologia
7.
BMC Cardiovasc Disord ; 22(1): 533, 2022 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-36476572

RESUMO

BACKGROUND: Shone's syndrome is a rare complex congenital anomaly. The classical definition consists of four anomalies: supravalvular mitral membrane, parachute mitral valve (PMV), subaortic stenosis, and coarctation of the aorta (CoA). Few studies have been reported on Shone's syndrome in adults, particularly the primary surgical correction of the anomalies. CASE PRESENTATION: A 22-year-old female patient presented with chest distress and tachypnea. Echocardiography and CT revealed supravalvular mitral membrane, PMV, Bicuspid aortic valve stenosis, CoA and patent ductus arteriosus. She underwent primary definitive surgical correction successfully and was discharged from hospital with symptoms free. CONCLUSIONS: Our case report highlights the importance of echocardiographic evaluation in the diagnosis of Shone's syndrome. The surgical strategy should be tailored according to both the patient's profile and the surgeon's personal surgical experience. Extra-anatomical bypass procedure is an appropriate technique for adult patients with long-segment coarctation and concomitant cardiac lesions. The outcomes of the case study indicate that the primary definitive surgery is encouraging.


Assuntos
Constrição Patológica , Adulto , Humanos , Adulto Jovem , Coartação Aórtica
8.
Cardiovasc Ultrasound ; 20(1): 16, 2022 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-35799201

RESUMO

Parachute mitral valve (PMV) is a common form of congenital mitral stenosis and is difficult to diagnose prenatally. This report describes a fetal case of PMV with coarctation of the aorta that was diagnosed at 25 weeks' gestation by echocardiography and confirmed at autopsy. We describe the ultrasonographic features in this case and present a useful sign for making a prenatal diagnosis of PMV.


Assuntos
Cardiopatias Congênitas , Estenose da Valva Mitral , Ecocardiografia , Feminino , Humanos , Valva Mitral/diagnóstico por imagem , Estenose da Valva Mitral/congênito , Estenose da Valva Mitral/diagnóstico por imagem , Gravidez , Diagnóstico Pré-Natal
9.
Langenbecks Arch Surg ; 407(1): 383-389, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34665326

RESUMO

BACKGROUND: The most appropriate venous reconstruction method remains debatable when a long section of portal vein (PV) and/or superior mesenteric vein (SMV) must be resected in patients undergoing a pancreaticoduodenectomy (PD). The aim of the present study was to describe the technical details of the parachute technique, a modified end-to-end anastomotic maneuver that can be used in the above-mentioned circumstances, and to investigate its safety and feasibility. STUDY DESIGN: Patients who underwent venous reconstruction using the parachute technique after receiving a PD with PV resection for pancreatic cancer between January 2014 and March 2019 were retrospectively reviewed. For the parachute technique, the posterior wall was sutured in a continuous fashion while the stitches were left untightened. The stitches were then tightened from both sides after the running suture of the posterior wall had been completed, thereby dispersing the tension applied to the stitched venous wall when the venous ends were brought together and solving any problems that would otherwise have been caused by over-tension. The postoperative outcomes and PV patency were then investigated. RESULTS: Fifteen patients were identified. The median length of the resected PV/SMV measured in vivo was 5 cm (range, 3-6 cm). The splenic vein was resected in all the patients and was reconstructed in 13 patients (87%). The overall postoperative complication rate (≥ Clavien-Dindo grade I) was 60%, while a major complication (≥ Clavien-Dindo grade IIIa) occurred in 1 patient (7%). No postoperative deaths occurred in this series. The PV patency at 1 year was 87%. CONCLUSION: The parachute technique is both safe and feasible and is a simple venous reconstruction procedure suitable for use in cases undergoing PD when the distance between the resected PV and SMV is relatively long.


Assuntos
Neoplasias Pancreáticas , Pancreaticoduodenectomia , Humanos , Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Veia Porta/cirurgia , Estudos Retrospectivos
10.
Afr Archaeol Rev ; 39(4): 461-477, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091573

RESUMO

Numerous doctoral degree holders were trained in African archaeometallurgy in the Global North as well as on the African continent. African archaeometallurgy continues to attract a significant number of researchers from Europe and North America. This paper is based on our lived experiences as resident African archaeometallurgists. We argue that out of frustration because of unequal power relations and lack of access to archaeological science laboratories and funding, most African archaeometallurgists are now pursuing other research areas and careers altogether. We propose some solutions to ensure sustainability in the training and practice of archaeological scientists on the African continent. We conclude that African scholars need to develop home-grown and long-term research capacities and strategies.


De nombreux docteurs ont été formés en archéométallurgie africaine dans le Nord global ainsi que sur le continent africain. L'archéométallurgie africaine continue d'attirer un nombre important de chercheurs d'Europe et d'Amérique du Nord. Cet article est basé sur nos expériences vécues en tant qu'archéométallurgistes africains résidents. Nous soutenons que, par frustration en raison des relations de pouvoir inégales et au manque d'accès aux laboratoires de sciences archéologiques et au financement, la plupart des archéométallurgistes africains poursuivent désormais d'autres domaines de recherche et carrières. Nous proposons quelques solutions pour assurer la pérennité de la formation et de la pratique des scientifiques archéologiques sur le continent africain. Nous concluons que les universitaires africains doivent développer des capacités et des stratégies de recherche locales et à long terme.

11.
BMC Cancer ; 21(1): 1021, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34521387

RESUMO

BACKGROUND: Clinical effectiveness and safety data of pazopanib in patients with advanced or mRCC in real-world setting from Asia Pacific, North Africa, and Middle East countries are lacking. METHODS: PARACHUTE is a phase IV, prospective, non-interventional, observational study. Primary endpoint was the proportion of patients remaining progression free at 12 months. Secondary endpoints were ORR, PFS, safety and tolerability, and relative dose intensity (RDI). RESULTS: Overall, 190 patients with a median age of 61 years (range: 22.0-96.0) were included. Most patients were Asian (70%), clear-cell type RCC was the most common (81%), with a favourable (9%), intermediate (47%), poor (10%), and unknown (34%) MSKCC risk score. At the end of the observational period, 78 patients completed the observational period and 112 discontinued the study; 60% of patients had the starting dose at 800 mg. Median RDI was 82%, with 52% of patients receiving < 85%. Of the 145 evaluable patients, 56 (39%) remained progression free at 12 months, and the median PFS was 10 months (95% CI: 8.48-11.83). 19% of patients (21/109) were long-term responders (on pazopanib for ≥18 months). The best response per RECIST 1.1 was CR/PR in 24%, stable disease in 44%, and PD in 31%. Most frequent (> 10%) TEAEs related to pazopanib included diarrhoea (30%), palmar-plantar erythrodysesthesia syndrome (15%), and hypertension (14%). CONCLUSIONS: Results of the PARACHUTE study support the use of pazopanib in patients with advanced or mRCC who are naive to VEGF-TKI therapy. The safety profile is consistent with that previously reported by pivotal and real-world evidence studies.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Indazóis/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Adulto , África do Norte , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Ásia , Carcinoma de Células Renais/etnologia , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Feminino , Humanos , Indazóis/administração & dosagem , Indazóis/efeitos adversos , Neoplasias Renais/etnologia , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Oriente Médio , Intervalo Livre de Progressão , Estudos Prospectivos , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Critérios de Avaliação de Resposta em Tumores Sólidos , Fatores de Risco , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
12.
Transfusion ; 61 Suppl 1: S223-S233, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34269457

RESUMO

BACKGROUND: Parachute airdrop offers a rapid transfusion supply option for humanitarian aid and military support. However, its impact on longer-term RBC survival is undocumented. This study aimed to determine post-drop quality of RBCs in concentrates (RCC), and both RBCs and plasma in whole blood (WB) during subsequent storage. STUDY DESIGN AND METHODS: Twenty-two units of leucodepleted RCC in saline, adenine, glucose, mannitol (SAGM) and 22 units of nonclinical issue WB were randomly allocated for air transportation, parachute drop, and subsequent storage (parachute), or simply storage under identical conventional conditions (4 ± 2°C) (control). All blood products were 6-8 days post-donation. Parachute units were packed into Credo Cubes, (Series 4, 16 L) inside a PeliCase (Peli 0350) and rigged as parachute delivery packs. Packs underwent a 4-h tactical flight (C130 aircraft), then parachuted from 250 to 400 ft before ground recovery. The units were sampled aseptically before and after airdrop at weekly intervals. A range of assays quantified the RBC storage lesion and coagulation parameters. RESULTS: Blood units were maintained at 2-6°C and recovered intact after recorded ground impacts of 341-1038 m s-2 . All units showed a classical RBC storage lesion and increased RBC microparticles during 42 days of storage. Fibrinogen and clotting factors decreased in WB during storage. Nevertheless, no significant difference was observed between Control and Parachute groups. Air transportation and parachute delivery onto land did not adversely affect, or shorten, the shelf life of fresh RBCs or WB. DISCUSSION: Appropriately packaged aerial delivery by parachute can be successfully used for blood supply.


Assuntos
Transfusão de Sangue , Eritrócitos/citologia , Plasma , Meios de Transporte , Preservação de Sangue , Humanos , Plasma/química , Indicadores de Qualidade em Assistência à Saúde
13.
Echocardiography ; 38(11): 1966-1969, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34672386

RESUMO

Parachute mitral valve (PMV) is a rare congenital cardiac valvular anomaly often associated with other congenital cardiac defects, particularly Shone's complex, but may infrequently occur in isolation. PMV and its variants are predominantly associated with mitral stenosis (MS) or rarely mitral regurgitation (MR). We present the case of a middle-aged female who was evaluated for a syncopal episode and found to have an atypical variant PMV with disproportionately long anterior mitral leaflet, bileaflet mitral valve prolapse, and mitral annular disjunction, without associated MS or MR. This is the first case report to highlight this particular constellation of findings.


Assuntos
Insuficiência da Valva Mitral , Prolapso da Valva Mitral , Estenose da Valva Mitral , Arritmias Cardíacas , Feminino , Humanos , Pessoa de Meia-Idade , Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/complicações , Insuficiência da Valva Mitral/diagnóstico por imagem , Prolapso da Valva Mitral/complicações , Prolapso da Valva Mitral/diagnóstico por imagem , Estenose da Valva Mitral/complicações , Estenose da Valva Mitral/diagnóstico por imagem
14.
J Card Surg ; 36(10): 3959-3962, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34338375

RESUMO

Parachute deformity of atrioventricular valve occurs when chordae tendineae arise either from one papillary muscle or a closely placed muscle group. Preoperative detection is easier with mitral involvement than with tricuspid valve. We present two cases of parachute tricuspid valve (PTV) which were successfully repaired.


Assuntos
Cordas Tendinosas , Valva Tricúspide , Cordas Tendinosas/diagnóstico por imagem , Cordas Tendinosas/cirurgia , Humanos , Músculos Papilares/diagnóstico por imagem , Músculos Papilares/cirurgia , Valva Tricúspide/diagnóstico por imagem , Valva Tricúspide/cirurgia
15.
J Card Surg ; 36(1): 333-335, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33085105

RESUMO

BACKGROUND: Parachute mitral valves (PMV) and parachute-like asymmetrical mitral valves (PLAMV) presenting in adulthood is rare. CASE REPORT: A 27-year-old primigravida, with 25 weeks of amenorrhea, presented with exertional dyspnea (NYHA class-2). She had a PLAMV, severe mitral stenosis, moderate central mitral regurgitation and pulmonary artery systolic pressure of 102 mm Hg. She underwent a successful valve repair. DISCUSSION: PMV/PLAMV and pregnancy present a dual challenge. In our case mitral repair resulted in a near-normal valve function and allowed our patient to safely carry her pregnancy to term.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Insuficiência da Valva Mitral , Estenose da Valva Mitral , Adulto , Dispneia , Feminino , Humanos , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/cirurgia , Estenose da Valva Mitral/diagnóstico por imagem , Estenose da Valva Mitral/cirurgia , Gravidez
16.
J Card Surg ; 36(1): 12-20, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33032391

RESUMO

BACKGROUND: Shone's complex is a rare lesion affecting the mitral valve (MV) and left ventricular outflow tract (LVOT). The objective of this study is to report the outcomes after Shone's complex repair, the growth of mitral and aortic valve and LVOT, and long-term survival. METHODS: This retrospective study included all patients diagnosed with Shone's complex, who underwent biventricular repair. Data including patients' characteristics, type of the MV lesion and the associated lesions were collected. Patients were followed up regularly with echocardiography, and the changes in mitral and aortic valve z-score and LVOT z-score were recorded. RESULTS: Thirty-seven patients were included in the study, the median age was 3.4 months, and 11 patients (30.6%) had pulmonary hypertension. The main procedure performed during the first surgical intervention was coarctation repair in 26 patients (70%). Twelve patients had MV repair, and five had MV replacement. Operative mortality occurred in 1 patient (2.7%), median follow up was 52 (25-75th percentile: 22-84) months. Survival at 1, 5, and 10 years was 94.4%, 90%, and 76.9%, respectively. Reoperation was required in 13 patients, mainly for LVOT repair (n = 8). Reoperation was significantly associated with associated aortic valve lesion (p = .044). The growth of the MV z-score was 0.35 per year; p < .001, aortic valve z-score 0.086 per year; p = 0.422, and the LVOT z-score was 0.53 per year; p = .01. CONCLUSION: Biventricular repair of Shone's complex has good outcomes. Reoperation is frequently encountered, especially with low aortic valve z-score. The MV and LVOT have significant growth following Shone's complex repair.


Assuntos
Cardiopatias Congênitas , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Seguimentos , Cardiopatias Congênitas/cirurgia , Humanos , Lactente , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Estudos Retrospectivos
17.
Toxicol Mech Methods ; 31(5): 393-399, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33784946

RESUMO

Gap junction intercellular communication (GJIC) is a necessary process for placental development. GJIC can be assessed with a parachute assay, where fluorescent dye-loaded donor cells are 'parachuted' onto acceptor cells and dye diffuses to adjacent cells with active GJIC. During co-culture, donor cells can attach, but the assay does not allow their distinction from acceptor cells, which presents as a major limitation. We have developed a modified parachute assay that permits distinction between donor and acceptor cells, using the extravillous trophoblast cell line HTR-8/SVneo and a lentiviral transduction technique. Using PKA activator CW008 as a positive control and 12-o-tetradecanoylphorbol-13-acetate as a negative control, this modified parachute assay reliably detects both enhanced and attenuated GJIC. Importantly, the ease and accuracy of quantification over currently available methods makes this modified assay optimal for automation and represents a useful tool for in vitro placental toxicological testing.


Assuntos
Junções Comunicantes , Placenta , Trofoblastos , Comunicação Celular , Comunicação , Feminino , Humanos , Gravidez
18.
Community Ment Health J ; 56(6): 1033-1043, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32036517

RESUMO

Guided by the principles of Open Dialogue and Intentional Peer Support (IPS), Parachute NYC was designed to provide a "soft landing" for people experiencing psychiatric crisis. From 2012 to 2018, Parachute's teams of clinicians and peer specialists provided home-based mental health care to enrollees and their networks (family, friends), seeking to engage and improve their natural support networks. This qualitative study examined the experiences of enrollees and network members who participated in Parachute. Participants reported that they valued the accessibility and flexibility of Parachute as well as their relationships with, and the lack of hierarchy within, the Parachute team. Responses to the structure of network meetings and Parachute's approach to medication were mixed, with a few participants struggling with what they felt was a lack of urgency and others experiencing the approach as holistic. Many enrollees and network members reported that Parachute improved their self-understanding and relationships with each other.


Assuntos
Aconselhamento , Grupo Associado , Humanos , Pesquisa Qualitativa , Rede Social , Especialização
19.
AAPS PharmSciTech ; 20(1): 20, 2019 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-30604109

RESUMO

SHetA2 is a novel anticancer drug with poor aqueous solubility. In formal toxicological studies, Kolliphor HS 15 was used as a solubilizing agent to increase the oral bioavailability of SHetA2. The purpose of this study was to formulate SHetA2 and Kolliphor HS 15 as solid powders to facilitate their filling in hard gelatin capsules for clinical trials. Two manufacturing processes, ultra-rapid freeze-drying (URFD) and spray freeze drying (SFD), were employed to fabricate solid powders of SHetA2-Kolliphor HS 15 and trehalose. The morphology, size, flowability, and compressibility of URFD-SHetA2 and SFD-SHetA2 powders were characterized. The crystallinity and apparent maximum solubility of SHetA2 in both powders were also determined. SFD-SHetA2 powders were spherical in shape, small, and with a wide size distribution while the URFD-SHetA2 powders were irregularly shaped and big but with a narrower distribution. DSC and XRD analyses indicated that SHetA2 was mostly amorphous in both powders. The flow of both powders was categorized as "good" (angle of repose < 35°). The uniformity of drug content in URFD-SHetA2 powders was more variable than that in SFD-SHetA2 powders. The solubility profile of SHetA2 in both powders SGF exhibited a transient supersaturation "spring effect" due to the drug's amorphousness followed by extended supersaturation "parachute effect" at approximately 6 µg/ml for both powders compared to 0.02 ± 0.01 µg/ml for unprocessed drug. In conclusion, both URFD and SFD formed solid SHetA2 Kolliphor powders that are possible formulation candidates to be filled in hard gelatin capsules for clinical trials.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacocinética , Cromanos/síntese química , Cromanos/farmacocinética , Tionas/síntese química , Tionas/farmacocinética , Administração Oral , Antineoplásicos/administração & dosagem , Disponibilidade Biológica , Cromanos/administração & dosagem , Dessecação , Liofilização/métodos , Ácido Gástrico/metabolismo , Humanos , Tamanho da Partícula , Pós , Solubilidade , Tionas/administração & dosagem , Difração de Raios X
20.
Artigo em Inglês | MEDLINE | ID: mdl-29425525

RESUMO

We report the techniques and long-term outcome of mitral valve (MV) repair to correct congenital mitral stenosis in children. Between 1986 and 2014, 137 children (mean age 4.1 ± 5.0, range 1 month-16.8 years) underwent repair of congenital mitral stenosis (CMS). In 48 patients, CMS is involved in Shone's anomaly. The typical congenital MS (type I) was seen in 56 patients. Hypoplastic MV (type II, n = 15) was associated with severe left ventricular outflow tract abnormalities and hypoplastic left ventricular cavity and muscle mass. Supravalvar ring (type III, n = 48) ranged from a thin membrane to a thick discrete fibrous ridge. Parachute MV (type IV, n = 10) have 2 leaflets and barely distinguishable commissures, but all chordae merged either into 1 major papillary muscle or asymmetric papillary muscles-1 dominant and the other minuscule. Hammock valve (type IV, n = 8) appeared dysplastic with shortened chordae directly inserted into the posterior left ventricular muscle mass. MV repair was performed using commissurotomy, chordal division, papillary muscle splitting and fenestration, and mitral ring resection, each applied according to the presenting morphology. During the 28-year follow-up period, 23 patients underwent repeat MV repair and 3 underwent MV replacement after failed attempts at repeat repair. At 1 and 15 years postoperatively, freedom from reoperation was 89.3 ± 5.1% and 52.8 ± 11.8%, and cumulative survival rates were 92.3 ± 4.3% and 70.3 ± 8.9, respectively. Mortality unrelated to repair accounted for 9 (20%) deaths. Long-term functional outcome of MV repair in children with CMS is satisfactory. Repeat repair or replacement may be deemed necessary during the course of follow-up.


Assuntos
Estenose da Valva Mitral/congênito , Estenose da Valva Mitral/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Estenose da Valva Mitral/mortalidade , Músculos Papilares/cirurgia , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
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