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1.
Hepatol Int ; 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32128704

RESUMO

BACKGROUND: Direct-acting anti-virals (DAAs) have markedly improved the effectiveness of anti-viral therapy for chronic hepatitis C (CHC) patients. In a phase III trial in Japan, treatment with the NS3/4A protease inhibitor glecaprevir and the NS5A inhibitor pibrentasvir (G/P) resulted in a small number of patients with refractory factors. We aimed to evaluate the effectiveness and safety of G/P, especially among patients with these refractory factors, and the influence of these factors on treatment. METHODS: In a prospective, multicenter study involving 33 medical institutions, 1439 patients were treated with G/P, and their efficacy, safety, and most frequent adverse effects (AEs) were analyzed. RESULTS: Overall SVR12 rates were 99.1% (1397/1410) in the per-protocol-analysis, and genotype sustained virologic response SVR12 rates were: genotype 1, 99.4% (707/711); genotype 2, 99.4% (670/674); genotype 3, 80.0% (16/20). DAA-naïve patients (p = 0.008) with HCV genotype except 3 (genotype 1 vs. 3, p = 2.68 × 10-5; genotype 2 vs. 3, p = 3.28 × 10-5) had significantly higher SVR12 rates. No significant difference was observed between CKD stage 1-3 (99.1% [1209/1220]) and chronic kidney disease (CKD) stage 4-5 (98.9% [188/190]) patients, or between cirrhotic (99.0% [398/402]) and non-cirrhotic (99.1% [999/1008]) patients. Multiple logistic regression analysis revealed that genotype 3 [OR 33.404, 95% CI (7.512-148.550), p value (p = 4.06 × 10-5)] and past experience of IFN-free DAAs [OR 3.977, 95% CI (1.153-13.725), p value (p = 0.029)] were both significantly independent predictors of non-SVR12. AEs were reported in 28.2% of patients, and 1.6% discontinued treatment owing to drug-related AEs. AEs were significantly higher in CKD stage 4-5 (41.6% [79/190]) than CKD stage 1-3 (26.1% [319/1220]) patients (p = 2.00 × 10-5). AEs were also significantly higher in cirrhotic (38.6% [155/402]) than in non-cirrhotic (24.1% [243/1008]) (p = 2.91 × 10-18) patients. CONCLUSIONS: G/P regimen is highly effective and safe to treat CHC patients even with refractory factors such as CKD and advanced liver fibrosis. However, patients with past experience of IFN-free DAA treatment and genotype 3, CKD stage 4 or 5, and advanced liver fibrosis should be more closely observed.

2.
Int J Pediatr Otorhinolaryngol ; 133: 109973, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32163824

RESUMO

OBJECTIVES: The auricle is a key target in pediatric plastic surgery and is considered to develop from a ring- or funnel-like arrangement of six hillocks in the embryo. However, there has been no report showing the morphologies of the auricular muscle and cartilage after midterm in humans. METHODS: We examined histological sections of 20 near-term human fetuses (29-40 weeks) and those from 7 midterm fetuses (15-16 weeks). RESULTS: At midterm, the auricular cartilage was a single wavy plate with the helicis major muscle (HMM). The superior and posterior auricular muscles (SAM, PAM) were inserted into the middle parts, and the anterior auricular muscle (AAM) was inserted into the lowest part of the cartilage plate, while the tragus and antitragus were not clearly identified. In near-term fetuses, the cartilage plate varied in size and shape between specimens. The scapha and antihelix were separated from the cartilage plate with major or minor involvement of the HMM from the initial mass along the helix. The SAM inserted to the crus helix or the developing scapha, while the insertion sites of the AAM and PAM into the helix were stable. The tragus-antitragus cartilages were well-developed and they sandwiched a deep notch of skin below the helix tail. The antitragicus muscle was more evident than the tragicus muscle. An unnamed muscle was evident along the external acoustic meatus. The other intrinsic muscles, including the transverse and oblique muscles, might develop from the HMM after birth. CONCLUSIONS: Development of the auricle was advanced after midterm. However, a single wavy plate-like cartilage was maintained until late-stage. Near term, the antihelix and scapha developed from the plate-like core of the auricle and the tragus and antitragus were added in the antero-inferior side of the cartilage plate. Establishment of muscle arrangements was markedly delayed compared to cartilage development. Altogether, the classical concept of an initial funnel-like arrangement of cartilage anlagen might have been biased by studies of adult morphology.

3.
Surg Radiol Anat ; 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32112281

RESUMO

A long tortuous course of the abducens nerve (ABN) crossing a highly curved siphon of the internal carotid artery is of interest to neurosurgeons for cavernous sinus surgery. Although a "straight" intracavernous carotid artery in fetuses can change into an adult-like siphon in infants, there is no information on when or how the unique course of ABN is established. Histological observations of 18 near-term fetuses (12 specimens of frontal sections and 6 specimens of sagittal sections) demonstrated the following: (I) the ABN consistently took a straight course crossing the lateral side of an almost straight intracavernous carotid artery; (II) the straight course was maintained when sympathetic nerves joined; (III) few parasellar veins of the developing cavernous sinus separated the ABN from the ophthalmic nerve; and (IV) immediately before the developing tendinous annulus for a common origin of extraocular recti, the ABN bent laterally to avoid a passage of the thick oculomotor nerve. Since the present observations strongly suggested morphologies at birth and in infants, major angulations of the ABN as well as the well-known course independent of the other nerves in the cavernous sinus seemed to be established during childhood. In the human body, the ABN might be a limited example showing a drastic postnatal change in course. Consequently, it might be important to know the unique course of ABN before performing endovascular interventions and skull base surgery for petroclival and cavernous sinus lesions without causing inadvertent neurovascular injuries to neonates or infants.

4.
Chembiochem ; 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32181563

RESUMO

There is great potential for siRNA in treatment of diseases through the reduction of damaging protein translation by RNA interference. However, delivery and cell uptake of siRNA poses a serious problem in its therapeutic applications. Methods to overcome this issue include chemical modification of the siRNA duplex to improve pharmacokinetics, stability and efficacy and conjugation to small ligand molecules to enable membrane penetration, targetability and potency. In this review, the most common modifications of siRNA will be discussed, along with ligand conjugates that are believed to be the most promising in advancing the field of targeted siRNA delivery.

5.
Chem Pharm Bull (Tokyo) ; 68(2): 129-132, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32009079

RESUMO

Efficient methods for delivery of antisense DNA or small interfering RNA (siRNA) are highly needed. Cationic materials, which are conventionally used for anionic oligonucleotide delivery, have several drawbacks, including aggregate formation, cytotoxicity and a low endosome escape efficiency. In this report a bio-reactive mask (i.e., disulfide unit) for cationic amino groups was introduced, and the mask was designed such that it was removed at the target cell surface. Insolubility and severe cellular toxicity caused by exposed cationic groups are avoided when using the mask. Moreover, the disulfide unit used to mask the cationic group enabled direct delivery of oligonucleotides to the cell cytosol. The molecular design reported is a promising approach for therapeutic applications.


Assuntos
DNA Antissenso/administração & dosagem , RNA Interferente Pequeno/administração & dosagem , Aminas/química , Animais , Cátions/química , DNA Antissenso/química , DNA Antissenso/genética , DNA Antissenso/farmacocinética , Dissulfetos/química , Inativação Gênica , Células HeLa , Humanos , Masculino , Camundongos Endogâmicos ICR , RNA Interferente Pequeno/química , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/farmacocinética , Transfecção/métodos
6.
Neurol Med Chir (Tokyo) ; 60(3): 136-146, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31902873

RESUMO

The histone H3K27M-mutant diffuse midline glioma is often seen in children and has a very poor prognosis regardless of its histological grade. Although it can occur in adults, few studies on adult cases have been reported. We examined adult midline glioma cases for their histological grade, presence of H3K27M mutation, and expression of related factors-enhancer of zeste homolog 2 (EZH2), H3K27me3, p16, and methylthioadenosine phosphorylase. These tumor characteristics were also evaluated for their prognostic value in adult midline glioma. High histological grade, H3K27M-mutant, high EZH2 expression, and high H3K27me3 expression was detected in 12/23 (53%), 11/23 (48%), 9/23 (39%), and 12/23 (52%) cases, respectively. Histological grade and prognosis were significantly correlated (P <0.01). The high expression of EZH2 and the low expression of H3K27me3 correlated with histological malignancy (P = 0.019 and 0.009) and prognosis (P = 0.048 and 0.047). To broaden the scope of our analysis, a review of cases reported in the literature (2014-2019) was performed. In the 171 cases, H3K27M-mutant showed poor prognosis in the young adult group (P = 0.001), whereas H3K27 status had no effect on prognosis in the older age group (P = 0.141). Histological grade was correlated with prognosis in both young adults and older groups (P <0.001, P = 0.003, respectively). We demonstrate differences in prognostic factors for diffuse gliomas in the midline region for children and adults. Importantly, the H3K27M mutation significantly influences prognosis in children, but not necessarily in adults. Contrarily, histological grading and immunostaining are important prognostic tools in adults.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31950525

RESUMO

BACKGROUND AND AIM: The presence of cirrhosis is an important factor for the management of patients with hepatitis C virus (HCV) infection and it determines the duration of treatment for HCV with the direct-acting antiviral (DAA) regimen of glecaprevir (GLE) and pibrentasvir (PIB), that is, 8 or 12 weeks, if patients do not have a history of DAA failure. However, in real-world settings, determination of cirrhosis depends on the discretion of the attending hepatologists, and it is unclear whether compensated cirrhosis was homogenously diagnosed or not. In this study, we investigated the real-world diagnosis of cirrhosis by characterizing DAA-naïve patients who underwent a 12-week GLE/PIB regimen in whom cirrhosis was diagnosed, comparing their characteristics with those of patients who underwent an 8-week regimen in whom cirrhosis was absent. METHODS: In a large, multicenter cohort study, we compared background characteristics and treatment outcomes among DAA-naïve patients who underwent an 8-week versus a 12-week GLE/PIB regimen. RESULTS: Among 977 patients enrolled, 296 (30.3%) were determined to have cirrhosis and underwent a 12-week regimen. Some patient characteristics largely overlapped between the two groups, including liver fibrosis indices. Sustained viral response rates were similar between groups after adjusting liver fibrosis index with propensity score matching. CONCLUSION: Although adequately diagnosed, the determination of cirrhosis varied widely among institutions or by hepatologists in real-world settings, and the severity of liver fibrosis overlapped significantly between patients in whom compensated cirrhosis was determined to be present and patients in whom cirrhosis was absent. Virologic efficacy was similar after adjusting for the degree of liver fibrosis.

8.
World Neurosurg ; 133: e281-e287, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31518739

RESUMO

BACKGROUND: The spot sign (SS) in spontaneous intracerebral hemorrhage has been reported to be a predictive factor of poor outcome; however, how SS is related with the clinical outcome remains unclear. We aimed to investigate how etiology associated with SS affects the clinical outcome of endoscopic surgery. METHODS: We retrospectively analyzed data from 104 patients (43 women and 61 men, mean age: 64.2 ± 11.0 years) who underwent endoscopic surgery for supratentorial intracerebral hemorrhage. The outcome variables analyzed were in-hospital mortality and modified Rankin scale score at 90 days from onset. RESULTS: The prevalence of intraventricular hemorrhage and the mean initial modified Graeb score were greater in SS-positive than in SS-negative patients (100% vs. 47.7%, P < 0.001, and 14.4 ± 5.4 vs. 10.6 ± 6.0, P = 0.03, respectively). Postoperative rebleeding occurred more frequently in SS-positive than -negative patients (25.0% vs. 6.8%, P = 0.045). The in-hospital mortality rate was 7.7% and was not significantly different between the groups (18.8% vs. 5.7%, P = 0.09). There was a significant unfavorable shift in modified Rankin scale scores at 90 days among SS-positive patients compared with SS-negative patients in an analysis with ordinal logistic regression (adjusted common odds ratio, 4.38; 95% confidence interval 0.06-0.79, P = 0.02). CONCLUSIONS: Intraventricular hemorrhage and postoperative rebleeding were considered to be associated with the poor outcome in patients with SS. The SS on computed tomography angiography may be valuable in predicting rebleeding and clinical outcome after surgery.


Assuntos
Hemorragia Cerebral/diagnóstico por imagem , Angiografia por Tomografia Computadorizada , Hematoma/diagnóstico por imagem , Neuroendoscopia , Idoso , Dano Encefálico Crônico/etiologia , Hemorragia Cerebral/complicações , Hemorragia Cerebral/cirurgia , Comorbidade , Feminino , Hematoma/complicações , Hematoma/cirurgia , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento
9.
RNA Biol ; 17(2): 264-280, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31601146

RESUMO

MicroRNAs (miRNAs) are small non-coding RNAs that play essential roles in the regulation of gene function by a mechanism known as RNA silencing. In a previous study, we revealed that miRNA-mediated silencing efficacy is correlated with the combinatorial thermodynamic properties of the miRNA seed-target mRNA duplex and the 5´-terminus of the miRNA duplex, which can be predicted using 'miScore'. In this study, a robust refined-miScore was developed by integrating the thermodynamic properties of various miRNA secondary structures and the latest thermodynamic parameters of wobble base-pairing, including newly established parameters for I:C base pairing. Through repeated random sampling and machine learning, refined-miScore models calculated with either melting temperature (Tm) or free energy change (ΔG) values were successfully built and validated in both wild-type and adenosine-to-inosine edited miRNAs. In addition to the previously reported contribution of the seed-target duplex and 5´-terminus region, the refined-miScore suggests that the central and 3´-terminus regions of the miRNA duplex also play a role in the thermodynamic regulation of miRNA-mediated silencing efficacy.

10.
World Neurosurg ; 134: e1037-e1046, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31759155

RESUMO

OBJECTIVE: The usefulness of endoscopic procedures for chronic subdural hematoma (CSDH) has been described, but the indications in patients of very advanced age have not been analyzed. The aim of this study was to evaluate the feasibility, safety, and usefulness of introduction of an endoscopic procedure for such patients. METHODS: We retrospectively analyzed the data of 540 CSDHs treated by burr-hole surgery with endoscopic examination. The safety of the endoscopic procedure was assessed according to postoperative complications, morbidity, and mortality. The outcome was evaluated by statistical comparison among 4 different age-groups, and the recurrence rate and risk factors for recurrence was investigated in patients of very advanced age. RESULTS: Postoperative complications occurred in 7 cases (1.5%). The 6-month morbidity and mortality were 13.5% and 4.5%. No complications, morbidity, or mortality associated with the additional endoscopic procedure occurred even in patients of very advanced age. The endoscopic features of trabecular structures and residual septa separating the cavity were also risk factors for recurrence in patients of very advanced age. Releasing of the septa showed the possibility of decreasing the risk of recurrence to 6.6% in patients aged ≥85 years as well as in younger patients. There were some inevitable problems such as prolongation of the surgical time and inadequate endoscopic surgical skill. CONCLUSIONS: An endoscopic procedure for CSDH can be safely indicated and useful even in patients aged ≥85 years. However, clinicians should carefully select the patients based on clinical information associated with risk factors for recurrence.

11.
Chem Commun (Camb) ; 56(3): 466-469, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31828267

RESUMO

We herein report a new approach for RNA interference, so-called "build-up RNAi" approach, where single-strand circular RNAs with a photocleavable unit or disulfide moiety were used as siRNA precursors. The advantages of using these circular RNA formats for RNAi were presented in aspects of immunogenicity and cellular uptake.


Assuntos
Interferência de RNA , Precursores de RNA/química , RNA Interferente Pequeno/química , Apolipoproteínas B/antagonistas & inibidores , Apolipoproteínas B/genética , Apolipoproteínas B/metabolismo , Precursores de RNA/síntese química , Precursores de RNA/efeitos da radiação , RNA Interferente Pequeno/metabolismo , Raios Ultravioleta
12.
Ann Anat ; 227: 151421, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31563572

RESUMO

PURPOSE: Our group had recently described human hand Pacinian corpuscles (PCs): the hand PCs are not simply arranged along the digital palmar nerves but often exhibited specific morphologies known uncommonly. However, there is still no or few information about human foot PCs. MATERIALS AND METHODS: We observed transverse sections of all five toes including the interdigital area obtained from 12 feet of eight fetuses at 28-33 weeks (crown-rump length 230-290mm). Serial sections were prepared for 3D reconstructions and measurement. RESULTS: Foot PCs were characterized by (1) a dense distribution in the interdigital area in contrast to a few PCs in the distal tip of the all five toes; (2) abundant dorsal PCs including those in the nail bed and: (3) a long chain of PCs in the flexor tendon sheath of all five toes. Therefore, a distal dominance was not evident in the foot in contrast to the hand and, a tendon sheath contained much greater numbers of PCs than the hand. A tree-like or bouquet-like arrangement of PCs along a short perforating artery to the palmar digital skin was seen in the foot as we had described in the hand. The tree of foot PCs was sometimes seen laying transversely along the digital skin surface, not toward the skin. CONCLUSION: It is still unknown that, in utero, how the PCs distribution became different between the hand and foot: it might be determined genetically in a region-specific manner.

13.
Anat Sci Int ; 95(2): 293-296, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31848973

RESUMO

A variation of the flexor carpi radialis with an excessive muscular bundle was found on the right forearm of a Japanese male cadaver. The flexor carpi radialis had two heads, medial one arising from the medial epicondyle of the humerus, and the other, a variant excessive muscular bundle, arising from the bicipital aponeurosis deep at the medial edge of the tendon of biceps brachii. There was also a muscular slip between the pronator teres and lateral head of flexor carpi radialis. The insertion of the ending tendon of the flexor carpi radialis was also variant, which was not only inserted into the base of the second metacarpal bone, but into the proximal surface of the scaphoid and the tubercle of trapezium. The excessive muscular bundle might be a residual muscular slip which connects between the distal part of the biceps brachii and the initial part of the flexor carpi radialis during the early embryonic development.

14.
Sci Adv ; 5(11): eaay0527, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31803839

RESUMO

Interfacing solid-state defect electron spins to other quantum systems is an ongoing challenge. The ground-state spin's weak coupling to its environment not only bestows excellent coherence properties but also limits desired drive fields. The excited-state orbitals of these electrons, however, can exhibit stronger coupling to phononic and electric fields. Here, we demonstrate electrically driven coherent quantum interference in the optical transition of single, basally oriented divacancies in commercially available 4H silicon carbide. By applying microwave frequency electric fields, we coherently drive the divacancy's excited-state orbitals and induce Landau-Zener-Stückelberg interference fringes in the resonant optical absorption spectrum. In addition, we find remarkably coherent optical and spin subsystems enabled by the basal divacancy's symmetry. These properties establish divacancies as strong candidates for quantum communication and hybrid system applications, where simultaneous control over optical and spin degrees of freedom is paramount.

15.
Science ; 366(6470): 1225-1230, 2019 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-31806809

RESUMO

Spin defects in silicon carbide have the advantage of exceptional electron spin coherence combined with a near-infrared spin-photon interface, all in a material amenable to modern semiconductor fabrication. Leveraging these advantages, we integrated highly coherent single neutral divacancy spins in commercially available p-i-n structures and fabricated diodes to modulate the local electrical environment of the defects. These devices enable deterministic charge-state control and broad Stark-shift tuning exceeding 850 gigahertz. We show that charge depletion results in a narrowing of the optical linewidths by more than 50-fold, approaching the lifetime limit. These results demonstrate a method for mitigating the ubiquitous problem of spectral diffusion in solid-state emitters by engineering the electrical environment while using classical semiconductor devices to control scalable, spin-based quantum systems.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31881554

RESUMO

BACKGROUND AND AIM: The prognosis of cirrhotic patients with hepatic edema is poor. Although several short-term predictors of tolvaptan (novel diuretic agent) treatment for such patients have been reported, the factors related to long-term survival are still unclear. METHODS: Among 459 patients with hepatic edema enrolled in a retrospective, multicenter collaborative study, we analyzed 407 patients who received tolvaptan. RESULTS: Patients consisted of 266 men and 141 women, with the median age of 68 years (range, 28-93 years). The frequency of short-term responders to tolvaptan was 59.7% (243/407). In the Cox regression analysis, short-term response to tolvaptan, low average dosages of furosemide and spironolactone during tolvaptan treatment, Child-Pugh classification A and B, and absence of hepatocellular carcinoma were independent factors contributed to 1-year survival. The 1-year and long-term cumulative survival rates in short-term responders were significantly higher than those in non-responders (P = 0.011 and 0.010, respectively). Using a receiver operating characteristic curve analysis, the optimal cut-off values of average daily dosages of furosemide and spironolactone for predicting 1-year survival were 19 and 23 mg/day, respectively. The long-term cumulative survival rates in patients who received a mean dosage of spironolactone < 23 mg/day during tolvaptan treatment were significantly higher than those receiving a mean dosage of ≥ 23 mg/day (P = 0.001). CONCLUSIONS: The present study suggests that the short-term response to tolvaptan and low dosages of conventional diuretics during tolvaptan treatment might improve the 1-year and long-term survival rates in cirrhotic patients with hepatic edema.

17.
Clin Imaging ; 60(1): 48-52, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31864199

RESUMO

BACKGROUND: Granulomatous amoebic encephalitis (GAE) is a rare and mostly fatal disease. Without specific symptoms, laboratory findings, or radiologic characteristics, establishing a correct diagnosis is challenging. In many cases of GAE, multiple ring-enhancing lesions with perifocal edema are observed on magnetic resonance imaging (MRI); a solitary and homogeneously enhancing mass masquerading as a malignant lymphoma that evolved into multiple hemorrhagic and necrotic lesions has rarely been reported in GAE. CASE DESCRIPTION: An immunocompetent 68-year-old man presented with transient right hemiparesis due to epilepsy. MRI revealed a well- and homogeneously enhancing mass with perifocal edema and restricted diffusion in the left parietal subcortical region. As malignant lymphoma was suspected based on MRI findings and an elevated ß2-microglobulin level in the cerebrospinal fluid, an open biopsy was performed; the pathological diagnosis was inconclusive but suggested a granulomatous disease. Although steroid therapy was administrated, subsequently the mass lesion gradually enlarged. After a second surgery for removal of the mass lesion, multiple hemorrhagic and necrotic lesions developed at the primary site and additionally in the brainstem. The patient entered a comatose state and died 3 months after admission. Histopathological examination and polymerase chain reaction analysis of the specimen revealed posthumously GAE caused by Balamuthia mandrillaris with necrotizing vasculitis. CONCLUSION: A solitary mass lesion initially mimicked a malignant lymphoma, and subsequently evolved into multiple hemorrhagic and necrotic lesions detected on T2*-weighted and susceptibility-weighted imaging. Such serial changes noted on MRI seem characteristic and suggestive of necrotizing vasculitis of GAE.

18.
Opt Lett ; 44(23): 5780-5783, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31774778

RESUMO

The doubly periodic Si photonic crystal waveguide operates as a nonmechanical beam-steering device that can be applied in light detection and ranging. In this Letter, we develop and describe a prism lens that collimates a fan-shaped beam, emitted from the waveguide independent of the steering angle. Its fundamental profile is investigated using a theoretical analysis for thick lenses, and then, its detailed aspherical design is obtained. In ray tracing, this prism lens suppresses the beam divergence to less than the diffraction limit in most of the targeted beam-steering range. The prism lens is fabricated by acrylic cutting, and its expected characteristics are observed.

19.
Clin Anat ; 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31659797

RESUMO

Histological examination of specimens from 22 donated elderly cadavers and 15 human fetuses revealed that the cricopharyngeus muscle (CPM) provided (1) posterior circular muscle fibers adjacent to the external aspect of the uppermost esophageal circular muscle and (2) a thin anterior sling connecting to that same muscle. Another thick lateral bundle of longitudinal muscle originated independently from a fascia covering the posterior cricoarytenoideus muscle, extended laterally and posteriorly, and occupied a space after the CPM had disappeared at the anterolateral angle of the esophagus below the cricoid. The thick fascia contained abundant elastic fibers along the internal surface of the pharyngeal constrictors (posteromedial elastic lamina), but was interrupted or discontinued near the cricoid origin of the CPM. As no submucosal smooth muscles or elastic fibers were connected to it, the CPM did not accompany a specific elastic structure at the interface between the pharyngeal and esophageal muscles. In fetuses, the medial half of the CPM was inserted into the cricoid while the lateral half continued to the sternothyroideus muscle or ended at a fascia covering the cricothyroideus. These anterolateral ends provided a mechanical load for longitudinal growth of the pharyngeal constrictors. Consequently, the CPM was unlikely to develop and grow to form the upper esophageal sphincter, and the muscle bundle crossing the lateral aspect of the pharyngo-esophageal junction appeared to have a secondary passive role as a sphincter. This situation contrasts with that of another sphincter in the human body formed from striated muscle. Clin. Anat., 2019. © 2019 Wiley Periodicals, Inc.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31609495

RESUMO

BACKGROUND: In clinical trials, a pangenotype direct-acting antiviral (DAA) regimen consisting of glecaprevir (GLE) and pibrentasvir (PIB) exhibited high virologic efficacy and tolerability in patients with hepatitis C virus (HCV) infection. This study sought to confirm these findings in real-world settings, focusing on patients with cirrhosis, history of DAA failure, or HCV genotype 3 who were treated with a 12-week regimen in a large multicenter study from Japan. METHODS: In a nationwide multicenter prospective cohort study, we analyzed background characteristics, tolerability, and treatment outcome of patients who underwent a 12-week GLE/PIB regimen. RESULTS: Of 1190 patients, 509 (42.8%) underwent the 12-week regimen, and the remaining patients underwent an 8-week regimen. The rate of sustained virologic response (SVR) of patients treated with the 12-week regimen was 99.0%, comparable with that of patients treated with the 8-week regimen. The adverse events were observed in 29.1% of patients. The main adverse event was pruritus, which was observed in 14.7%. Ten patients (2.0%) discontinued therapy during treatment period. CONCLUSION: The 12-week GLE/PIB regimen was well-tolerated with high virologic efficacy in patients with cirrhosis, experience of DAA, or HCV genotype 3; tolerability and SVR rate were comparable with those of DAA-naïve, non-cirrhotic, non-genotype 3 patients who underwent 8-week regimen.

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