Basal tearing is crucial to maintaining ocular surface wetness. Corneal cold thermoreceptors sense small oscillations in ambient temperature and change their discharge accordingly. Deletion of the ...cold-transducing ion channel Transient receptor potential cation channel subfamily M member 8 (TRPM8) in mice abrogates cold responsiveness and reduces basal tearing without affecting nociceptor-mediated irritative tearing. Warming of the cornea in humans also decreases tearing rate. These findings indicate that TRPM8-dependent impulse activity in corneal cold receptors contributes to regulating basal tear flow.
Piezoelectric materials, a type of “smart” material that generates electricity while deforming and vice versa, have been used extensively for many important implantable medical devices such as ...sensors, transducers, and actuators. However, commonly utilized piezoelectric materials are either toxic or nondegradable. Thus, implanted devices employing these materials raise a significant concern in terms of safety issues and often require an invasive removal surgery, which can damage directly interfaced tissues/organs. Here, we present a strategy for materials processing, device assembly, and electronic integration to 1) create biodegradable and biocompatible piezoelectric PLLA poly(L-lactic acid) nanofibers with a highly controllable, efficient, and stable piezoelectric performance, and 2) demonstrate device applications of this nanomaterial, including a highly sensitive biodegradable pressure sensor for monitoring vital physiological pressures and a biodegradable ultrasonic transducer for blood–brain barrier opening that can be used to facilitate the delivery of drugs into the brain. These significant applications, which have not been achieved so far by conventional piezoelectric materials and bulk piezoelectric PLLA, demonstrate the PLLA nanofibers as a powerful material platform that offers a profound impact on various medical fields including drug delivery, tissue engineering, and implanted medical devices.
Background
Stereotactic body radiation therapy (SBRT) is a promising option for patients with pancreatic cancer (PCA); however, limited data support its efficacy. This study reviews our institutional ...experience of SBRT in the treatment of locally advanced (LAPC) and borderline resectable (BRPC) PCA.
Methods
Charts of all PCA patients receiving SBRT at our institution from 2010 to 2014 were reviewed. Most patients received pre-SBRT chemotherapy. Primary endpoints included overall survival (OS) and local progression-free survival (LPFS). Patients received a total dose of 25–33 Gy in five fractions.
Results
A total of 88 patients were included in the analysis, 74 with LAPC and 14 with BRPC. The median age at diagnosis was 67.2 years, and median follow-up from date of diagnosis for LAPC and BRPC patients was 14.5 and 10.3 months, respectively. Median OS from date of diagnosis was 18.4 months (LAPC, 18.4 mo; BRPC, 14.4 mo) and median PFS was 9.8 months (95 % CI 8.0–12.3). Acute toxicity was minimal with only three patients (3.4 %) experiencing acute grade ≥3 toxicity. Late grade ≥2 gastrointestinal toxicity was seen in five patients (5.7 %). Of the 19 patients (21.6 %) who underwent surgery, 79 % were LAPC patients and 84 % had margin-negative resections.
Conclusions
Chemotherapy followed by SBRT in patients with LAPC and BRPC resulted in minimal acute and late toxicity. A large proportion of patients underwent surgical resection despite limited radiographic response to therapy. Further refinements in the integration of chemotherapy, SBRT, and surgery might offer additional advancements toward optimizing patient outcomes.
Remdesivir was recently approved by the Food and Drug Administration for the treatment of hospitalized patients with coronavirus disease 2019 (COVID-19). Remdesivir is the prodrug of an adenosine ...analogue that inhibits viral replication of several RNA virus families, including
Preclinical data in animal models of coronavirus diseases, including COVID-19, have demonstrated that early treatment with remdesivir leads to improved survival, decreased lung injury, and decreased levels of viral RNA. Recent clinical data have demonstrated the clinical activity of remdesivir in terms of faster time to recovery in patients with severe COVID-19 and higher odds of improved clinical status in patients with moderate COVID-19. Here, clinical trials published to date are presented and appraised. Remdesivir's potential benefits and its favorable adverse-event profile make it an option for the treatment of COVID-19. This article examines the available literature describing remdesivir's pharmacology, pharmacokinetics, and preclinical and clinical data.
When the ocular surface of one eye is inflamed or injured, its corneal sensory nerve activity is modified, which in turn evokes ocular discomfort, irritation, and pain sensations referred to the ...affected eye. Some patients with unilateral ocular inflammation, infection, or surgery also report discomfort and pain in the contralateral eye. Are these sensations experienced at the fellow eye due to alterations of its sensory nerve activity?
To test this hypothesis, we recorded in vitro the activity of corneal mechanonociceptor, polymodal nociceptor and cold thermoreceptor nerves of both eyes of guinea pigs previously subjected unilaterally to three different experimental inflammatory and lesion conditions: UV‐induced photokeratitis, microkeratome corneal surgery, and chronic tear deficiency caused by removal of the main lacrimal gland. Recordings from the eyes of naïve animals were used as control.
Compared with the naïve guinea pigs, animals subjected to unilateral UV‐induced mild corneal inflammation, showed inhibition of the spontaneous and stimulus‐evoked activity of cold thermoreceptors, and increased activity (sensitization) of nociceptors affecting both the ipsilateral and the contralateral eye. Unilateral microkeratome surgery affected the activity of nociceptors mostly, inducing sensitization in both eyes. Chronic eye dryness by removal of the main lacrimal gland increased cold thermoreceptor activity in both eyes. These results show that after unilateral eye damage, corneal sensory nerve activity is altered in both eyes, although to a lesser degree in the contralateral eye.
This is the first direct demonstration that unilateral corneal nerve insult, and especially ocular surface inflammation, functionally affects the activity of the different types of corneal sensory nerves in both the ipsilateral and contralateral eyes. The mechanisms underlying the changes of contralateral sensory nerve activity remain to be determined, although available data support the involvement of the immune system. The present results have two main implications: (a) contralateral eyes cannot be considered as a control in experimental designs of both preclinical and clinical studies; and, (b) clinicians must consider the convenience of treating both eyes of patients with unilateral ocular conditions to avoid pain and secondary undesirable effects in the fellow eye.
Subgenus
Nothofagus, although geographically restricted at present to temperate areas of South America, has captured much attention in discussions of plant biogeography due to its widespread ...distribution through Gondwanan continents during the Tertiary. However, phylogenetic relationships within the subgenus
Nothofagus have not yet been resolved. We examined geographic patterns of intraspecific and interspecific genetic variation to detect whether incongruences in nuclear or plastid DNA phylogenies occur, in order to better understand the evolutionary history of the subgenus
Nothofagus. We conducted spatially-explicit sampling at 10 distinct locations throughout the range of austral South American forests and sampled all present
Nothofagus species. We used ITS and chloroplast DNA sequences to estimate phylogenetic relationships. A phylogeny constructed from nuclear genes resolved the subgenus
Nothofagus as monophyletic. We found that
N. antarctica was a sister to a clade of evergreen species (
N. betuloides,
N. dombeyi, and
N. nitida), while
N. pumilio likely diverged earlier. Nine cpDNA haplotypes were distinguished in the subgenus
Nothofagus which were associated to geographic locations rather than to taxonomic relationships. This species-independent cpDNA phylogeographic structures within the subgenus
Nothofagus may be related to repeated chloroplast capture events over geological time in Patagonia.
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