Nanotechnology is science, engineering, and technology conducted at the nanoscale, which is about 1 to 100 nanometers. It has led to the development of nanomaterials, which behave very differently compared with materials with larger scales and can be applied in a wide range of applications in biomedicine. The physical and chemical properties of materials of such small compounds depend mainly on the size, shape, composition, and functionalisation of the system. Nanoparticles, carbon nanotubes, liposomes, polymers, dendrimers, nanogels, among others, can be nanoengineeried for controlling all parameters, including their functionalisation with ligands, which provide the desired interaction with the immunological system. However, undesired issues related to their toxicity and hypersensitivity responses have impeded more rapid health applications. Through interactions with the immune system, some of these nanostructures show promising applications as vaccines and diagnostics tools. Dendrimeric Antigens, Nanoallergens, and nanoparticles are potential tools for the in vitro diagnosis of allergic reactions. Glycodendrimers, liposomes, polymers, and nanoparticles have shown interesting applications in immunotherapy. There are wide panels of structures accessible, and controlling their physico-chemical properties would allow the obtainment of safer and more efficient compounds for clinical applications goals, either in diagnosis or treatment.
Background: Open living donor hepatectomy (OLDH) is a highly painful procedure. Advanced strategies for enhancing perioperative analgesia and accelerating recovery are needed for patients undergoing OLDH. This study evaluated the effects of intravenous infusion of dexmedetomidine (DEX) during OLDH on postoperative analgesia and recovery. Methods: This prospective, randomized, double-blinded, and placebo-controlled study included 34 patients randomized to a control group (group C) and a DEX group (group D). Utilization of intravenous patient-controlled analgesia (IV-PCA) pump, pain intensity, and postoperative recovery variables were recorded. Moreover, intraoperative anesthetic consumption, hemodynamic parameters, and fluid status were also recorded. Results: During the first 24 hours after surgery, patients in group D had a lower pain intensity. The cumulative numbers of IV-PCA pump presses and fentanyl consumption within 24 and 48 hours postoperatively in group C were significantly higher than in group D. The time to first IV-PCA attempt was prolonged in group D. In addition, faster flatus passage was observed in group D. Intraoperatively, fewer anesthetic agents were required in group D. Less fluctuation in hemodynamics and reduced bleeding were also found in group D. Conclusions: The present study revealed that the addition of intravenous infusion of DEX during OLDH provided several benefits in relieving postoperative pain and promoting recovery. Therefore, we concluded that intraoperative DEX infusion may play an important role in enhancing recovery of patients undergoing OLDH.
In the survivorship setting, adolescent and young adult (AYA) cancer survivors frequently demonstrate little knowledge of infertility risk, are unclear regarding their fertility status and may under- or over-estimate their treatment-related risk for infertility. In female AYA survivors, ovarian function usually parallels fertility, and can be assessed with serum hormone levels and ultrasonography. Post-treatment fertility preservation may be appropriate for survivors at risk for primary ovarian insufficiency. In male AYA survivors, fertility and gonadal function are not always equally affected, and can be assessed with a semen analysis and serum hormones, respectively. As reproductive health issues are commonly cited as an important concern by survivors of AYA cancer, multidisciplinary care teams including oncology, endocrinology, psychology, and reproductive medicine are advocated, with the aim of optimal provision of fertility advice and care for AYA cancer survivors.
Rhombencephalitis refers to inflammatory diseases of the rhombencephalon. The encephalitic processes located to the rhombencephalon are frequently associated with Listeria monocytogenes and enterovirus infections. We report a case of community-acquired Klebsiella Pneumoniae systemic infection with CNS involvement in an adult patient without significant comorbidities.
A patient with Birt-Hogg-Dubé Syndrome (BHDS) developed metastatic follicular thyroid cancer, which until now has never been described in someone with BHDS. Thyroid cancer is not currently recommended for screening with BHDS. This case presents implications for future guidelines and planning for renal transplant in patients with this condition.
The investigation of ecological processes that maintain species coexistence is important in harsh environments, as they act as strong drivers of species selection. Congeneric species are a good model to investigate the relative importance of such processes, as closely related species tend to have similar niches. We aim to find evidence for the action and relative importance of different ecological processes hypothesized to maintain species coexistence in a tropical forest subject to seasonal flooding, using the spatial structure of populations of three congeneric species. We collected data on a 1-ha plot of a Brazilian white-sand flooded tropical forest, where individuals of three Myrcia species were tagged, mapped, and measured for diameter at soil height. We also sampled seven environmental variables in the plot. We employed several spatial point pattern models to simultaneously investigate habitat filtering, interspecific competition, stochasticity, and dispersal limitation. Habitat filtering was the most important process driving the local distribution of the species, as they showed associations, albeit of different strength, to environmental variables related to flooding. We did not detect spatial patterns consistent with interspecific competition, i.e. spatial segregation and smaller size of nearby congeners. The three species do not seem to show evidence of stochasticity even though congeners were spatially independent, since they responded to differences in the environment. Last, dispersal limitation only led to spatial associations of different size classes for one of the species. Using data from congeneric species in a harsh environment as a model, we demonstrated that habitat filtering to areas subject to flooding is the most important ecological process driving the local distribution of the species studied in a white-sand forest. Even though many studies on topo-edaphic variation in tropical forests have shown that habitat filtering is an important ecological process, other processes that drive community structuring may have gone undetected.
Through this case, we present the thought process, team-based strategy and sequel of managing a complex, critically ill pregnant with ARDS and COVID-19 pneumonia. This case also confirms the feasibility of using convalescent plasma and ECMO during early postnatal period in acutely ill parturient with respiratory failure.
Objectives: To investigate the effect of NBI examination on the differentiating between benign and malignant neoplasms involving nasal cavity. Design, Setting, Participants: A retrospective case series from January 2018 to December 2019 were performed at a single center. A total of 188 consecutive patients who were first diagnosed with lesions in unilateral nasal cavity underwent complete examination with white light endoscopy (WLE) and NBI endoscopy, respectively. Biopsy was harvested from the target lesion and sent to the pathologist for definite diagnosis. Participants with a history of congenital malformation, trauma and surgery in nasal cavity were excluded from the study. Main outcome measures: Endoscopic diagnosis was assessed using sensitivity, specificity, accuracy and positive and negative predictive values (PPV and NPV, respectively). Results: In identifying benign and malignant lesions of nasal cavity, NBI had a significant higher sensitivity (92.7% vs 70.7%, P = 0.020) and NPV (98% vs 92.3%, P = 0.032) than WLE, but there were no significant differences between NBI and WLE in specificity (98.6% vs 97.3%, P = 0.684), accuracy (97.3% vs 91.5%, P = 0.416) and PPV (95% vs 87.9%, P = 0.400). Conclusion: The emerging technique of NBI can improve the diagnostic accuracy of distinguishing benign and malignant lesions in nasal cavity, and remains a promising and helpful adjunct to the traditional endoscopy techniques.
A 70-year-old diabetic woman was admitted to our hospital with a complaint of high fever accompanying shaking chills for three days. The patient had no abdominal symptoms and no history of eating raw food. The patient’s body temperature was increased to 39 oC, and blood analysis showed elevations of leukocytes (17,400 /µL) and C-reactive protein (16.5 mg/dL). Computed tomography revealed air density spots in the aortic wall (Fig A ), and Salmonella enteritidis serotype O9 was detected by blood culture. Under a tentative diagnosis of Salmonella-induced infective aortic aneurysm, the patient underwent antibiotic treatment with ampicillin/sulbactam. On day 11, the air had disappeared and the aortic wall showed a varicose deformity, leading to a differential diagnosis of infective aortic aneurysm (Fig B ). The patient recovered completely with 8-week antibiotic therapy without any operation.Cases of infective aortic aneurysms account for only about 1% to 3% of total cases of aortic aneurysm. However, the case fatality has been reported to be as high as 18 percent in two years1, and an early diagnosis is essential. Salmonella species are known as a common pathogen of the crucial infection2, and so clinicians should pay attention to the development of the disease.
Experience and training in field work is a critical component of undergraduate education in ecology, and many university courses incorporate field-based or experiential components into the curriculum in order to provide students hands-on experience. Due to the onset of the COVID-19 pandemic and the sudden shift to remote instruction in the spring of 2020, many instructors of such courses found themselves struggling to identify strategies for developing rigorous field activities that could be completed online, solo, and from a student’s backyard. This case study illustrates the process by which one field-based course, a UC California Naturalist certification course offered at the University of California, Davis, transitioned to fully remote instruction. The transition relied on established, publicly available, online participatory science platforms (e.g., iNaturalist) to which the students contributed data and observations remotely. Student feedback on the course and voluntary continued engagement with the participatory science platforms indicates that the student perspective of the experience was on par with previous traditional offerings of the course. This case study also includes topics and participatory science resources for consideration by other faculty facing a similar transition from group field activities to remote, individual field-based experiences.
COVID-19 created a host of challenges for science education; in our case, the pandemic halted our in-person elementary school outreach project on bird biology. This project was designed as a year-long program to teach fifth grade students in Ithaca, New York, USA about bird ecology and biodiversity, using outdoor demonstrations and in-person games and activities to engage students in nature. As a central part of this effort, we set up nest boxes on school property and had planned to monitor them with students during bird breeding in the spring. Here, we describe our experiences transitioning this program online: we live streamed nest boxes to students’ virtual classrooms and used them as starting points for virtual lessons on bird breeding and nestling development. We suggest that instituting similar programs at local schools can promote equitable learning opportunities for students across geographical locations and with various living situations. In an era of social distancing and isolation, we propose that nest box live streaming and virtual lessons can support local communities by providing access to the outdoors and unconventional science learning opportunities for all students.
The first drug specific for cystic fibrosis (CF) was approved in 1993, and since then several other drugs have been approved. Median predicted survival in people with CF has improved from approximately 30 years to 44.4 years over that same period. In 2020, highly-effective modulators of the cystic fibrosis transmembrane conductance regulator became available to approximately 90% of people with CF ages 12 years and older. These transformative therapies will surely reduce morbidity and further extend longevity. The drug development pipeline is filled with therapies that address most aspects of CF disease. As survival and CF therapies have advanced, and the complexity of CF care increases, the process of drug development has become more sophisticated. In addition, detecting meaningful changes in clinical outcomes has become more difficult as the health status of people with CF improves. Design of clinical trials in CF has become more complex, and innovative approaches are required to continue to advance drug development. This review provides a general overview of drug development from the pre-clinical phase through Phase IV. Special considerations with respect to CF are integrated into the discussion of each phase of drug development. The dawn of a new era has arrived for people with CF. As CF care evolves, drug development must continue to evolve as well, until a one-time cure is available to all people with CF.
Both 5q-linked spinal muscular atrophy (SMA) and Duchenne muscular dystrophy (DMD) are fatal monogenic neuromuscular disorders caused by loss-of-function mutations. SMA is an autosomal recessive disorder affecting motor neurons that is typically caused by homozygous whole-gene deletions of SMN1. DMD is an X-linked recessive muscle disease most often due to exon deletions, but also duplications and smaller sized variants within the DMD gene. Gene replacement therapy offers the opportunity to correct the underlying genetic defect by the introduction of a functional gene. We review the transformative work from clinical trials to United States Food and Drug Administration approval of onasemnogene abeparvovec-xioi in SMA and its application in clinical practice and the early results of microdystrophin delivery in DMD. We also review the introduction of antisense oligonucleotides to alter pre-mRNA splicing to promote exon inclusion (as in nusinersen in SMA) or exclusion (as in eteplirsen in DMD) into neuromuscular therapeutics. There are multiple promising novel genetically mediated therapies on the horizon, which in aggregate point towards a hopeful future for individuals with SMA and DMD.
Team-Based Learning (TBL) is a pedagogical tool that has great potential to develop student engagement, accountability, and equity in the online classroom. TBL is rooted in evidence-based educational theories and practices that underlie many active learning approaches such as self-testing, team discussion, and application of knowledge. The use of these approaches is associated with better student performance, retention, and sense of belonging in the classroom, aspects that are often reported to be especially lacking in online courses. Here, we describe how we implemented TBL in a face-to-face and an online introductory level evolution and biodiversity course. Our experiences using TBL approaches in the online course have been rewarding, students are engaged and accountable for their learning, and performed well in the course. Our goal is to provide an example of how we designed a life science course using TBL approaches and transitioned the course to an online environment. With the current switch to remote instruction and online learning, we recommend the use of TBL as a course design approach that can improve the students online learning experience.
Abstract Background Differentiating viral from bacterial acute respiratory infections (ARIs) remains challenging, due to the non-specific clinical manifestations. The COVID-19 pandemic is putting extraordinary strain on healthcare resources. To date, molecular testing is available but has a long turnaround time and therefore cannot provide results at the point-of-care (POC) thereby exposing COVID-19/Non-COVID-19 patients to each other while awaiting diagnosis. Methods This observational study prospectively evaluated the utility of a triage strategy including FebriDx, a POC fingerstick blood test that differentiates viral from bacterial ARIs through simultaneous detection of Myxovirus-resistance protein A (MxA) and C-reactive protein (CRP), in rapidly determining viral cases requiring immediate isolation and confirmatory molecular testing, from non-infectious patients or bacterial infections requiring antibiotics. Results 75 consecutive patients were screened, 48 eligible cases were tested with FebriDx, 36 were confirmed viral infection and 35/36 had COVID-19. 31/35 COVID-19 cases tested positive for SARS-CoV-2 via rRT-PCR and (4/35) had a clinical diagnosis of probable COVID-19 based on symptoms, epidemiological history, and chest imaging (PPV 100% (35/35)). 13 cases were FebriDx viral negative and rRT-PCR was also negative. In one case, it was not possible to determine the exact cause of infection, although a viral infection could not be excluded. Including this patient, FebriDx NPV was 92.3% (12/13), exceeding the NPV of rRT-PCR a 68.3% (13/19), and diagnostic sensitivity was conservatively calculated at 97% (35/36) compared to 82.9% (29/35) for initial rRT-PCR. The diagnostic specificity of both FebriDx and rRT-PCR was 100%. Conclusions: FebriDx could be deployed as part of a reliable triage strategy for identifying possible COVID-19 patients with symptomatic ARI in the COVID-19 pandemic. Key words: Pandemic; COVID-19; SARS-CoV-2; pneumonia; viral; point of care; infection
Chronic Granulomatous Disease (CGD) is a rare inherited disorder in which phagocytes lack NADPH oxidase activity. The most common form is the X-linked CGD (X-CGD), caused by mutations in the CYBB gene. Clinical, functional and genetic characterizations of 16 CGD cases of male patients and their relatives were done. We classified them as suffering from different variants of CGD (X910, X91− or X91+) according to NOX2 expression and NADPH oxidase activity in neutrophils. Twelve mutations were novel (10 X910-CGD and 2 X91− -CGD). One X910-CGD was due to a new and extremely rare double missense mutation Thr208Arg-Thr503Ile. We investigated the pathological impact of each single using stable transfection of each mutated cDNA in the NOX2 knock-out PLB-985 cell line. Both mutations leading to X91−-CGD were also novel; one deletion -67delT was localized in the promoter region of CYBB, the second one c.253-1879A>G mutation activates a splicing donor site, which unveils a cryptic acceptor site, leading to the inclusion of a 124-nucleotide pseudo-exon between exons 3 and 4 and responsible for the partial loss of NOX2 expression. Both X91−-CGD mutations were characterized by a low cytochrome b558 expression and a faint NADPH oxidase activity. The functional impact of new missense mutations is discussed in the context of a new 3D-model of the dehydrogenase domain of NOX2. Our study demonstrates that low NADPH oxidase activity found in both X91−-CGD patients correlates with mild clinical forms of CGD whereas X910-CGD and X91+-CGD cases remain the most clinically severe forms.